SMAD2 is a receptor-regulated SMAD transcription factor that transduces activin, Nodal and TGF-beta signals. Activated type I receptors phosphorylate its C-terminal serines, enabling association with SMAD4 and other SMADs, nuclear accumulation, and context-dependent transcription with partners such as FOXH1. SMAD2 binds DNA directly when properly folded; the exon-3-encoded E3 insert in the long isoform regulates its conformation and affinity, while the shorter isoform lacks this insert. SMAD2 cycles between cytosol and nucleus, and its phosphorylation, ubiquitination and interactions with phosphatases regulate signal duration. Its outputs include embryonic mesendoderm specification, epithelial remodeling and tissue differentiation; vascular BMP9 responses and miRNA-processing functions represent additional contexts.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000785 chromatin | IDA PMID:21828274 HEB and E2A function as SMAD/FOXH1 cofactors. | ACCEPT | Summary: SMAD-containing transcription complexes occupy chromatin at regulatory loci; human embryonic stem-cell and endoderm assays support this location. Reason: SMAD-containing transcription complexes occupy chromatin at regulatory loci; human embryonic stem-cell and endoderm assays support this location. Supporting Evidence: PMID:21828274 We identified a new motif, termed SMAD complex-associated (SCA), that is bound by SMAD2/3/4 and FOXH1 in human embryonic stem cells (hESCs) and derived endoderm. |
| GO:0000785 chromatin | ISA GO_REF:0000113 | ACCEPT | Summary: SMAD-containing transcription complexes occupy chromatin at regulatory loci; human embryonic stem-cell and endoderm assays support this location. Reason: SMAD-containing transcription complexes occupy chromatin at regulatory loci; human embryonic stem-cell and endoderm assays support this location. Supporting Evidence: PMID:21828274 We identified a new motif, termed SMAD complex-associated (SCA), that is bound by SMAD2/3/4 and FOXH1 in human embryonic stem cells (hESCs) and derived endoderm. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: Sequence-specific binding at RNA polymerase II regulatory elements is directly supported. Reason: Sequence-specific binding at RNA polymerase II regulatory elements is directly supported. In SMAD2, the E3 insert modulates intrinsic binding; the 2019 human protein experiments overturn the blanket claim that the full-length protein cannot bind DNA. Supporting Evidence: PMID:31582430 The SMAD2 MH1 domain and full-length proteins also bound to different 5GC probes (Gsc1 and Gsc2 probes) from the Gsc promoter in the 0.6β1.2 Β΅M concentration range |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IDA PMID:31582430 Structural basis for distinct roles of SMAD2 and SMAD3 in FO... | ACCEPT | Summary: Sequence-specific binding at RNA polymerase II regulatory elements is directly supported. Reason: Sequence-specific binding at RNA polymerase II regulatory elements is directly supported. In SMAD2, the E3 insert modulates intrinsic binding; the 2019 human protein experiments overturn the blanket claim that the full-length protein cannot bind DNA. Supporting Evidence: PMID:31582430 The SMAD2 MH1 domain and full-length proteins also bound to different 5GC probes (Gsc1 and Gsc2 probes) from the Gsc promoter in the 0.6β1.2 Β΅M concentration range |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IDA PMID:9389648 Dual role of the Smad4/DPC4 tumor suppressor in TGFbeta-indu... | ACCEPT | Summary: Sequence-specific binding at RNA polymerase II regulatory elements is directly supported. Reason: Sequence-specific binding at RNA polymerase II regulatory elements is directly supported. In SMAD2, the E3 insert modulates intrinsic binding; the 2019 human protein experiments overturn the blanket claim that the full-length protein cannot bind DNA. Supporting Evidence: PMID:31582430 The SMAD2 MH1 domain and full-length proteins also bound to different 5GC probes (Gsc1 and Gsc2 probes) from the Gsc promoter in the 0.6β1.2 Β΅M concentration range |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IBA GO_REF:0000033 | ACCEPT | Summary: DNA-binding and context-dependent activation or repression identify a bona fide RNA polymerase II transcription factor; recruitment often involves partner transcription factors rather than autonomous high-affinity binding. Reason: DNA-binding and context-dependent activation or repression identify a bona fide RNA polymerase II transcription factor; recruitment often involves partner transcription factors rather than autonomous high-affinity binding. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:21828274 We identified a new motif, termed SMAD complex-associated (SCA), that is bound by SMAD2/3/4 and FOXH1 in human embryonic stem cells (hESCs) and derived endoderm. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | ISA GO_REF:0000113 | ACCEPT | Summary: DNA-binding and context-dependent activation or repression identify a bona fide RNA polymerase II transcription factor; recruitment often involves partner transcription factors rather than autonomous high-affinity binding. Reason: DNA-binding and context-dependent activation or repression identify a bona fide RNA polymerase II transcription factor; recruitment often involves partner transcription factors rather than autonomous high-affinity binding. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:21828274 We identified a new motif, termed SMAD complex-associated (SCA), that is bound by SMAD2/3/4 and FOXH1 in human embryonic stem cells (hESCs) and derived endoderm. |
| GO:0000987 cis-regulatory region sequence-specific DNA binding | IC PMID:21828274 HEB and E2A function as SMAD/FOXH1 cofactors. | MODIFY | Summary: Sequence-specific regulatory double-stranded DNA binding is supported by the properly folded human protein; refine to the existing RNA polymerase II cis-regulatory sequence-specific binding term. Reason: Sequence-specific regulatory double-stranded DNA binding is supported by the properly folded human protein; refine to the existing RNA polymerase II cis-regulatory sequence-specific binding term. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:31582430 The SMAD2 MH1 domain and full-length proteins also bound to different 5GC probes (Gsc1 and Gsc2 probes) from the Gsc promoter in the 0.6β1.2 Β΅M concentration range |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IDA PMID:31582430 Structural basis for distinct roles of SMAD2 and SMAD3 in FO... | ACCEPT | Summary: Signal-induced SMAD complexes activate target transcription. Reason: Signal-induced SMAD complexes activate target transcription. This activity does not imply ligand-independent transcription or that SMAD2 must lack the exon-3 insert. Supporting Evidence: PMID:9311995 Smads 2, 3 and 4 accumulated in the nucleus upon TGF-beta1 treatment in Mv1Lu cells, and showed a synergistic effect in a transcriptional reporter assay using the TGF-beta-inducible plasminogen activator inhibitor-1 promoter. PMID:31582430 The SMAD2 MH1 domain and full-length proteins also bound to different 5GC probes (Gsc1 and Gsc2 probes) from the Gsc promoter in the 0.6β1.2 Β΅M concentration range |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IDA PMID:9389648 Dual role of the Smad4/DPC4 tumor suppressor in TGFbeta-indu... | ACCEPT | Summary: Signal-induced SMAD complexes activate target transcription. Reason: Signal-induced SMAD complexes activate target transcription. This activity does not imply ligand-independent transcription or that SMAD2 must lack the exon-3 insert. Supporting Evidence: PMID:9311995 Smads 2, 3 and 4 accumulated in the nucleus upon TGF-beta1 treatment in Mv1Lu cells, and showed a synergistic effect in a transcriptional reporter assay using the TGF-beta-inducible plasminogen activator inhibitor-1 promoter. PMID:31582430 The SMAD2 MH1 domain and full-length proteins also bound to different 5GC probes (Gsc1 and Gsc2 probes) from the Gsc promoter in the 0.6β1.2 Β΅M concentration range |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IEA GO_REF:0000120 | ACCEPT | Summary: Signal-induced SMAD complexes activate target transcription. Reason: Signal-induced SMAD complexes activate target transcription. This activity does not imply ligand-independent transcription or that SMAD2 must lack the exon-3 insert. Supporting Evidence: PMID:9311995 Smads 2, 3 and 4 accumulated in the nucleus upon TGF-beta1 treatment in Mv1Lu cells, and showed a synergistic effect in a transcriptional reporter assay using the TGF-beta-inducible plasminogen activator inhibitor-1 promoter. PMID:31582430 The SMAD2 MH1 domain and full-length proteins also bound to different 5GC probes (Gsc1 and Gsc2 probes) from the Gsc promoter in the 0.6β1.2 Β΅M concentration range |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | ISS PMID:24964035 Pin1 promotes degradation of Smad proteins and their interac... | ACCEPT | Summary: Signal-induced SMAD complexes activate target transcription. Reason: Signal-induced SMAD complexes activate target transcription. This activity does not imply ligand-independent transcription or that SMAD2 must lack the exon-3 insert. Supporting Evidence: PMID:9311995 Smads 2, 3 and 4 accumulated in the nucleus upon TGF-beta1 treatment in Mv1Lu cells, and showed a synergistic effect in a transcriptional reporter assay using the TGF-beta-inducible plasminogen activator inhibitor-1 promoter. PMID:31582430 The SMAD2 MH1 domain and full-length proteins also bound to different 5GC probes (Gsc1 and Gsc2 probes) from the Gsc promoter in the 0.6β1.2 Β΅M concentration range |
| GO:0001657 ureteric bud development | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: The traced donor study documents Smad expression during kidney development and explicitly frames functional roles as speculation. Reason: The traced donor study documents Smad expression during kidney development and explicitly frames functional roles as speculation. Expression alone does not establish SMAD2 participation specifically in ureteric bud development. Supporting Evidence: PMID:14656760 Based on the observed patterns of expression, we speculate that individual or combinations of Smads may play specific roles in cell-fate determination during kidney development. |
| GO:0001707 mesoderm formation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Mesoderm formation and patterning are specific developmental outputs of Nodal/SMAD2 transcription; distinguish lineage allocation from an assertion that SMAD2 mechanically builds the tissue. Reason: Mesoderm formation and patterning are specific developmental outputs of Nodal/SMAD2 transcription; distinguish lineage allocation from an assertion that SMAD2 mechanically builds the tissue. Supporting Evidence: PMID:15084457 selective removal of both Smad2 and Smad3 from the epiblast additionally disrupts specification of axial and paraxial mesodermal derivatives. PMID:12842913 graded Nodal/Smad2 signals govern allocation of the axial mesendoderm precursors that selectively give rise to the ADE and PCP mesoderm. |
| GO:0003002 regionalization | IEA GO_REF:0000117 | MODIFY | Summary: The broad patterning claim is supported by specific anterior/posterior patterning and organizer lineage allocation. Reason: The broad patterning claim is supported by specific anterior/posterior patterning and organizer lineage allocation. Refine to anterior/posterior pattern specification already present. Proposed replacements: anterior/posterior pattern specification Supporting Evidence: PMID:12842913 graded Nodal/Smad2 signals govern allocation of the axial mesendoderm precursors that selectively give rise to the ADE and PCP mesoderm. |
| GO:0003140 determination of left/right asymmetry in lateral mesoderm | IMP PMID:17239842 The left-right axis is regulated by the interplay of Coco, X... | UNDECIDED | Summary: The cited study examines Xenopus left-right signaling through Coco, Xnr1 and derriere. Reason: The cited study examines Xenopus left-right signaling through Coco, Xnr1 and derriere. The cached abstract does not expose the SMAD2-specific manipulation or construct; do not infer a wrong-gene assignment or a direct human laterality experiment from that limitation. Supporting Evidence: PMID:17239842 Formation of the left-right axis involves a symmetry-breaking signal originating in the node or its equivalents, which increases TGF-beta signaling on the left side of the embryo and ultimately leads to asymmetric patterning of the viscera. |
| GO:0003180 aortic valve morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Genetic reduction of Smad2 in Adamts5-null mice increases aortic and pulmonary valve abnormalities and impairs cushion excavation, independently supporting these transferred developmental roles. Reason: Genetic reduction of Smad2 in Adamts5-null mice increases aortic and pulmonary valve abnormalities and impairs cushion excavation, independently supporting these transferred developmental roles. Supporting Evidence: PMID:23531444 faulty versican clearance due to ADAMTS5 deficiency blocks the initiation of pSmad2 signaling, which is required for excavation of endocardial cushions during aortic and pulmonary valve development. |
| GO:0003180 aortic valve morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Genetic reduction of Smad2 in Adamts5-null mice increases aortic and pulmonary valve abnormalities and impairs cushion excavation, independently supporting these transferred developmental roles. Reason: Genetic reduction of Smad2 in Adamts5-null mice increases aortic and pulmonary valve abnormalities and impairs cushion excavation, independently supporting these transferred developmental roles. Supporting Evidence: PMID:23531444 faulty versican clearance due to ADAMTS5 deficiency blocks the initiation of pSmad2 signaling, which is required for excavation of endocardial cushions during aortic and pulmonary valve development. |
| GO:0003184 pulmonary valve morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Genetic reduction of Smad2 in Adamts5-null mice increases aortic and pulmonary valve abnormalities and impairs cushion excavation, independently supporting these transferred developmental roles. Reason: Genetic reduction of Smad2 in Adamts5-null mice increases aortic and pulmonary valve abnormalities and impairs cushion excavation, independently supporting these transferred developmental roles. Supporting Evidence: PMID:23531444 faulty versican clearance due to ADAMTS5 deficiency blocks the initiation of pSmad2 signaling, which is required for excavation of endocardial cushions during aortic and pulmonary valve development. |
| GO:0003184 pulmonary valve morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Genetic reduction of Smad2 in Adamts5-null mice increases aortic and pulmonary valve abnormalities and impairs cushion excavation, independently supporting these transferred developmental roles. Reason: Genetic reduction of Smad2 in Adamts5-null mice increases aortic and pulmonary valve abnormalities and impairs cushion excavation, independently supporting these transferred developmental roles. Supporting Evidence: PMID:23531444 faulty versican clearance due to ADAMTS5 deficiency blocks the initiation of pSmad2 signaling, which is required for excavation of endocardial cushions during aortic and pulmonary valve development. |
| GO:0003203 endocardial cushion morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Genetic reduction of Smad2 in Adamts5-null mice increases aortic and pulmonary valve abnormalities and impairs cushion excavation, independently supporting these transferred developmental roles. Reason: Genetic reduction of Smad2 in Adamts5-null mice increases aortic and pulmonary valve abnormalities and impairs cushion excavation, independently supporting these transferred developmental roles. Supporting Evidence: PMID:23531444 faulty versican clearance due to ADAMTS5 deficiency blocks the initiation of pSmad2 signaling, which is required for excavation of endocardial cushions during aortic and pulmonary valve development. |
| GO:0003203 endocardial cushion morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Genetic reduction of Smad2 in Adamts5-null mice increases aortic and pulmonary valve abnormalities and impairs cushion excavation, independently supporting these transferred developmental roles. Reason: Genetic reduction of Smad2 in Adamts5-null mice increases aortic and pulmonary valve abnormalities and impairs cushion excavation, independently supporting these transferred developmental roles. Supporting Evidence: PMID:23531444 faulty versican clearance due to ADAMTS5 deficiency blocks the initiation of pSmad2 signaling, which is required for excavation of endocardial cushions during aortic and pulmonary valve development. |
| GO:0003677 DNA binding | IDA PMID:9389648 Dual role of the Smad4/DPC4 tumor suppressor in TGFbeta-indu... | MODIFY | Summary: Direct DNA binding is supported, but the RNA polymerase II cis-regulatory sequence-specific binding term already present is more informative. Reason: Direct DNA binding is supported, but the RNA polymerase II cis-regulatory sequence-specific binding term already present is more informative. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:31582430 The SMAD2 MH1 domain and full-length proteins also bound to different 5GC probes (Gsc1 and Gsc2 probes) from the Gsc promoter in the 0.6β1.2 Β΅M concentration range |
| GO:0003677 DNA binding | IEA GO_REF:0000107 | MODIFY | Summary: Direct DNA binding is supported, but the RNA polymerase II cis-regulatory sequence-specific binding term already present is more informative. Reason: Direct DNA binding is supported, but the RNA polymerase II cis-regulatory sequence-specific binding term already present is more informative. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:31582430 The SMAD2 MH1 domain and full-length proteins also bound to different 5GC probes (Gsc1 and Gsc2 probes) from the Gsc promoter in the 0.6β1.2 Β΅M concentration range |
| GO:0003682 chromatin binding | IEA GO_REF:0000107 | ACCEPT | Summary: Chromatin association is a central step in transcriptional signal output and is demonstrated independently of soluble DNA affinity. Reason: Chromatin association is a central step in transcriptional signal output and is demonstrated independently of soluble DNA affinity. Supporting Evidence: PMID:21828274 We identified a new motif, termed SMAD complex-associated (SCA), that is bound by SMAD2/3/4 and FOXH1 in human embryonic stem cells (hESCs) and derived endoderm. |
| GO:0003690 double-stranded DNA binding | IEA GO_REF:0000120 | MODIFY | Summary: Sequence-specific regulatory double-stranded DNA binding is supported by the properly folded human protein; refine to the existing RNA polymerase II cis-regulatory sequence-specific binding term. Reason: Sequence-specific regulatory double-stranded DNA binding is supported by the properly folded human protein; refine to the existing RNA polymerase II cis-regulatory sequence-specific binding term. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:31582430 The SMAD2 MH1 domain and full-length proteins also bound to different 5GC probes (Gsc1 and Gsc2 probes) from the Gsc promoter in the 0.6β1.2 Β΅M concentration range |
| GO:0003690 double-stranded DNA binding | ISS GO_REF:0000024 | MODIFY | Summary: Sequence-specific regulatory double-stranded DNA binding is supported by the properly folded human protein; refine to the existing RNA polymerase II cis-regulatory sequence-specific binding term. Reason: Sequence-specific regulatory double-stranded DNA binding is supported by the properly folded human protein; refine to the existing RNA polymerase II cis-regulatory sequence-specific binding term. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:31582430 The SMAD2 MH1 domain and full-length proteins also bound to different 5GC probes (Gsc1 and Gsc2 probes) from the Gsc promoter in the 0.6β1.2 Β΅M concentration range |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:17438144 Smad7 antagonizes transforming growth factor beta signaling ... | MODIFY | Summary: The experimentally supported activity acts on RNA polymerase II target genes; refine to the already annotated polymerase-specific transcription factor activity. Reason: The experimentally supported activity acts on RNA polymerase II target genes; refine to the already annotated polymerase-specific transcription factor activity. Proposed replacements: DNA-binding transcription factor activity, RNA polymerase II-specific Supporting Evidence: PMID:9311995 Smads 2, 3 and 4 accumulated in the nucleus upon TGF-beta1 treatment in Mv1Lu cells, and showed a synergistic effect in a transcriptional reporter assay using the TGF-beta-inducible plasminogen activator inhibitor-1 promoter. |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:9389648 Dual role of the Smad4/DPC4 tumor suppressor in TGFbeta-indu... | MODIFY | Summary: The experimentally supported activity acts on RNA polymerase II target genes; refine to the already annotated polymerase-specific transcription factor activity. Reason: The experimentally supported activity acts on RNA polymerase II target genes; refine to the already annotated polymerase-specific transcription factor activity. Proposed replacements: DNA-binding transcription factor activity, RNA polymerase II-specific Supporting Evidence: PMID:9311995 Smads 2, 3 and 4 accumulated in the nucleus upon TGF-beta1 treatment in Mv1Lu cells, and showed a synergistic effect in a transcriptional reporter assay using the TGF-beta-inducible plasminogen activator inhibitor-1 promoter. |
| GO:0005160 transforming growth factor beta receptor binding | IPI PMID:9311995 TGF-beta receptor-mediated signalling through Smad2, Smad3 a... | MODIFY | Summary: The direct receptor partner is the TGF-beta type I receptor; refine to the type I receptor-binding term already present. Reason: The direct receptor partner is the TGF-beta type I receptor; refine to the type I receptor-binding term already present. This is substrate docking, not kinase activity of SMAD2. Proposed replacements: type I transforming growth factor beta receptor binding Supporting Evidence: PMID:8980228 MADR2 and not the related protein DPC4 transiently interacts with the TGFbeta receptor and is directly phosphorylated by the complex on C-terminal serines. |
| GO:0005515 protein binding | IPI PMID:10615055 Structural basis of Smad2 recognition by the Smad anchor for... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:10615055. Assayed/reported partner: UniProtKB:O95405. |
| GO:0005515 protein binding | IPI PMID:11278756 Ski-interacting protein interacts with Smad proteins to augm... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:11278756. Assayed/reported partner: UniProtKB:Q13573. |
| GO:0005515 protein binding | IPI PMID:11387212 The adaptor molecule Disabled-2 links the transforming growt... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:11387212. Assayed/reported partner: UniProtKB:P98082. |
| GO:0005515 protein binding | IPI PMID:11779503 Crystal structure of a phosphorylated Smad2. Recognition of ... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:11779503. Assayed/reported partner: UniProtKB:Q13485. |
| GO:0005515 protein binding | IPI PMID:12764135 The transforming activity of Ski and SnoN is dependent on th... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:12764135. Assayed/reported partner: UniProtKB:P12757-1. |
| GO:0005515 protein binding | IPI PMID:15107821 c-Ski inhibits the TGF-beta signaling pathway through stabil... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:15107821. Assayed/reported partner: UniProtKB:P12755. |
| GO:0005515 protein binding | IPI PMID:15231748 Functional proteomics mapping of a human signaling pathway. | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:15231748. Assayed/reported partner: UniProtKB:O95405. |
| GO:0005515 protein binding | IPI PMID:15231748 Functional proteomics mapping of a human signaling pathway. | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:15231748. Assayed/reported partner: UniProtKB:P12757. |
| GO:0005515 protein binding | IPI PMID:15231748 Functional proteomics mapping of a human signaling pathway. | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:15231748. Assayed/reported partner: UniProtKB:Q12955. |
| GO:0005515 protein binding | IPI PMID:15231748 Functional proteomics mapping of a human signaling pathway. | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:15231748. Assayed/reported partner: UniProtKB:Q13485. |
| GO:0005515 protein binding | IPI PMID:15231748 Functional proteomics mapping of a human signaling pathway. | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:15231748. Assayed/reported partner: UniProtKB:Q9HAU4. |
| GO:0005515 protein binding | IPI PMID:15350224 Structural basis of heteromeric smad protein assembly in TGF... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:15350224. Assayed/reported partner: UniProtKB:Q13485. |
| GO:0005515 protein binding | IPI PMID:15647271 The integral inner nuclear membrane protein MAN1 physically ... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:15647271. Assayed/reported partner: UniProtKB:Q9Y2U8. |
| GO:0005515 protein binding | IPI PMID:16200078 Cloning and functional characterization of a new Ski homolog... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:16200078. Assayed/reported partner: UniProtKB:Q2VWA4. |
| GO:0005515 protein binding | IPI PMID:16751101 PPM1A functions as a Smad phosphatase to terminate TGFbeta s... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:16751101. Assayed/reported partner: UniProtKB:P35813. |
| GO:0005515 protein binding | IPI PMID:17099224 Potentiation of Smad-mediated transcriptional activation by ... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:17099224. Assayed/reported partner: UniProtKB:Q93062. |
| GO:0005515 protein binding | IPI PMID:17292623 Fussel-15, a novel Ski/Sno homolog protein, antagonizes BMP ... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:17292623. Assayed/reported partner: UniProtKB:P84550. |
| GO:0005515 protein binding | IPI PMID:18268325 IKKalpha is a critical coregulator of a Smad4-independent TG... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:18268325. Assayed/reported partner: UniProtKB:O15111. |
| GO:0005515 protein binding | IPI PMID:18511908 Identification of PCTA, a TGIF antagonist that promotes PML ... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:18511908. Assayed/reported partner: UniProtKB:O95405. |
| GO:0005515 protein binding | IPI PMID:18511908 Identification of PCTA, a TGIF antagonist that promotes PML ... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:18511908. Assayed/reported partner: UniProtKB:Q13485. |
| GO:0005515 protein binding | IPI PMID:18568018 TAZ controls Smad nucleocytoplasmic shuttling and regulates ... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:18568018. Assayed/reported partner: UniProtKB:Q9GZV5. |
| GO:0005515 protein binding | IPI PMID:18729074 Identification of novel Smad2 and Smad3 associated proteins ... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:18729074. Assayed/reported partner: UniProtKB:O00308. |
| GO:0005515 protein binding | IPI PMID:18729074 Identification of novel Smad2 and Smad3 associated proteins ... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:18729074. Assayed/reported partner: UniProtKB:P12755. |
| GO:0005515 protein binding | IPI PMID:18729074 Identification of novel Smad2 and Smad3 associated proteins ... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:18729074. Assayed/reported partner: UniProtKB:P84022. |
| GO:0005515 protein binding | IPI PMID:18729074 Identification of novel Smad2 and Smad3 associated proteins ... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:18729074. Assayed/reported partner: UniProtKB:Q13485. |
| GO:0005515 protein binding | IPI PMID:18729074 Identification of novel Smad2 and Smad3 associated proteins ... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:18729074. Assayed/reported partner: UniProtKB:Q13573. |
| GO:0005515 protein binding | IPI PMID:18729074 Identification of novel Smad2 and Smad3 associated proteins ... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:18729074. Assayed/reported partner: UniProtKB:Q9BZ29. |
| GO:0005515 protein binding | IPI PMID:18729074 Identification of novel Smad2 and Smad3 associated proteins ... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:18729074. Assayed/reported partner: UniProtKB:Q9HAU4. |
| GO:0005515 protein binding | IPI PMID:18832382 HMGA2 and Smads co-regulate SNAIL1 expression during inducti... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:18832382. Assayed/reported partner: UniProtKB:P52926. |
| GO:0005515 protein binding | IPI PMID:18923419 An Id-like molecule, HHM, is a synexpression group-restricte... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:18923419. Assayed/reported partner: UniProtKB:Q8TAK6. |
| GO:0005515 protein binding | IPI PMID:19032343 Ski co-repressor complexes maintain the basal repressed stat... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:19032343. Assayed/reported partner: UniProtKB:P12755. |
| GO:0005515 protein binding | IPI PMID:19049980 SKI and MEL1 cooperate to inhibit transforming growth factor... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:19049980. Assayed/reported partner: UniProtKB:Q9HAZ2. |
| GO:0005515 protein binding | IPI PMID:19122240 Pin1 down-regulates transforming growth factor-beta (TGF-bet... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:19122240. Assayed/reported partner: UniProtKB:Q13526. |
| GO:0005515 protein binding | IPI PMID:19135894 FAM/USP9x, a deubiquitinating enzyme essential for TGFbeta s... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:19135894. Assayed/reported partner: UniProtKB:Q13485. |
| GO:0005515 protein binding | IPI PMID:19135894 FAM/USP9x, a deubiquitinating enzyme essential for TGFbeta s... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:19135894. Assayed/reported partner: UniProtKB:Q9UPN9. |
| GO:0005515 protein binding | IPI PMID:19289081 Nuclear export of Smad2 and Smad3 by RanBP3 facilitates term... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:19289081. Assayed/reported partner: UniProtKB:Q9H6Z4. |
| GO:0005515 protein binding | IPI PMID:19345189 A Mutant-p53/Smad complex opposes p63 to empower TGFbeta-ind... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:19345189. Assayed/reported partner: UniProtKB:P04637. |
| GO:0005515 protein binding | IPI PMID:19345189 A Mutant-p53/Smad complex opposes p63 to empower TGFbeta-ind... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:19345189. Assayed/reported partner: UniProtKB:Q9H3D4. |
| GO:0005515 protein binding | IPI PMID:20061380 MTMR4 attenuates transforming growth factor beta (TGFbeta) s... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:20061380. Assayed/reported partner: UniProtKB:Q9NYA4. |
| GO:0005515 protein binding | IPI PMID:20129061 TMEPAI, a transmembrane TGF-beta-inducible protein, sequeste... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:20129061. Assayed/reported partner: UniProtKB:Q969W9. |
| GO:0005515 protein binding | IPI PMID:20195357 A comprehensive resource of interacting protein regions for ... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:20195357. Assayed/reported partner: UniProtKB:P05060. |
| GO:0005515 protein binding | IPI PMID:20195357 A comprehensive resource of interacting protein regions for ... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:20195357. Assayed/reported partner: UniProtKB:P05412. |
| GO:0005515 protein binding | IPI PMID:20195357 A comprehensive resource of interacting protein regions for ... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:20195357. Assayed/reported partner: UniProtKB:P07197. |
| GO:0005515 protein binding | IPI PMID:20195357 A comprehensive resource of interacting protein regions for ... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:20195357. Assayed/reported partner: UniProtKB:P61586. |
| GO:0005515 protein binding | IPI PMID:20195357 A comprehensive resource of interacting protein regions for ... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:20195357. Assayed/reported partner: UniProtKB:Q12955. |
| GO:0005515 protein binding | IPI PMID:20195357 A comprehensive resource of interacting protein regions for ... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:20195357. Assayed/reported partner: UniProtKB:Q96KR1. |
| GO:0005515 protein binding | IPI PMID:20211142 An atlas of combinatorial transcriptional regulation in mous... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:20211142. Assayed/reported partner: UniProtKB:Q13485. |
| GO:0005515 protein binding | IPI PMID:20603019 TIF1gamma controls erythroid cell fate by regulating transcr... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:20603019. Assayed/reported partner: UniProtKB:Q9UPN9. |
| GO:0005515 protein binding | IPI PMID:20937913 Coupling of tandem Smad ubiquitination regulatory factor (Sm... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:20937913. Assayed/reported partner: UniProtKB:Q9HAU4. |
| GO:0005515 protein binding | IPI PMID:21258410 Selective targeting of activating and inhibitory Smads by di... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:21258410. Assayed/reported partner: UniProtKB:O00308. |
| GO:0005515 protein binding | IPI PMID:21297662 Homeodomain protein DLX4 counteracts key transcriptional con... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:21297662. Assayed/reported partner: UniProtKB:Q13485. |
| GO:0005515 protein binding | IPI PMID:21532621 Nodal enhances the activity of FoxO3a and its synergistic in... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:21532621. Assayed/reported partner: UniProtKB:Q13485. |
| GO:0005515 protein binding | IPI PMID:21599657 ZNF580, a novel C2H2 zinc-finger transcription factor, inter... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:21599657. Assayed/reported partner: UniProtKB:Q9UK33. |
| GO:0005515 protein binding | IPI PMID:21741598 A Pin1/mutant p53 axis promotes aggressiveness in breast can... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:21741598. Assayed/reported partner: UniProtKB:Q9H3D4. |
| GO:0005515 protein binding | IPI PMID:21947082 USP15 is a deubiquitylating enzyme for receptor-activated SM... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:21947082. Assayed/reported partner: UniProtKB:Q9Y4E8. |
| GO:0005515 protein binding | IPI PMID:21960005 PPM1A dephosphorylates RanBP3 to enable efficient nuclear ex... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:21960005. Assayed/reported partner: UniProtKB:Q9H6Z4. |
| GO:0005515 protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:21988832. Assayed/reported partner: UniProtKB:P84022. |
| GO:0005515 protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:21988832. Assayed/reported partner: UniProtKB:Q13485. |
| GO:0005515 protein binding | IPI PMID:22045334 Ablation of Smurf2 reveals an inhibition in TGF-Ξ² signalling... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:22045334. Assayed/reported partner: UniProtKB:Q9HAU4. |
| GO:0005515 protein binding | IPI PMID:22442258 Intercellular variation in signaling through the TGF-Ξ² pathw... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:22442258. Assayed/reported partner: UniProtKB:P12755. |
| GO:0005515 protein binding | IPI PMID:22442258 Intercellular variation in signaling through the TGF-Ξ² pathw... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:22442258. Assayed/reported partner: UniProtKB:Q13485. |
| GO:0005515 protein binding | IPI PMID:24627487 C18 ORF1, a novel negative regulator of transforming growth ... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:24627487. Assayed/reported partner: UniProtKB:O15165. |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:25241761. Assayed/reported partner: UniProtKB:P04637. |
| GO:0005515 protein binding | IPI PMID:25609649 Proteomic analyses reveal distinct chromatin-associated and ... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:25609649. Assayed/reported partner: UniProtKB:P05412. |
| GO:0005515 protein binding | IPI PMID:25609649 Proteomic analyses reveal distinct chromatin-associated and ... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:25609649. Assayed/reported partner: UniProtKB:Q13485. |
| GO:0005515 protein binding | IPI PMID:25670079 14-3-3ΞΆ turns TGF-Ξ²'s function from tumor suppressor to meta... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:25670079. Assayed/reported partner: UniProtKB:P04637. |
| GO:0005515 protein binding | IPI PMID:26977879 Inhibiting Drivers of Non-mutational Drug Tolerance Is a Sal... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:26977879. Assayed/reported partner: UniProtKB:P12755. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:32296183. Assayed/reported partner: UniProtKB:O75593. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:33961781. Assayed/reported partner: UniProtKB:O95405. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:33961781. Assayed/reported partner: UniProtKB:P12755. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:33961781. Assayed/reported partner: UniProtKB:P12757. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:33961781. Assayed/reported partner: UniProtKB:P84022. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:33961781. Assayed/reported partner: UniProtKB:Q13485. |
| GO:0005515 protein binding | IPI PMID:35512704 Systematic discovery of mutation-directed neo-protein-protei... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:35512704. Assayed/reported partner: UniProtKB:Q13485. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:40205054. Assayed/reported partner: UniProtKB:Q13485. |
| GO:0005515 protein binding | IPI PMID:9389648 Dual role of the Smad4/DPC4 tumor suppressor in TGFbeta-indu... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:9389648. Assayed/reported partner: UniProtKB:O75593. |
| GO:0005515 protein binding | IPI PMID:9389648 Dual role of the Smad4/DPC4 tumor suppressor in TGFbeta-indu... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:9389648. Assayed/reported partner: UniProtKB:P70056. |
| GO:0005515 protein binding | IPI PMID:9389648 Dual role of the Smad4/DPC4 tumor suppressor in TGFbeta-indu... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:9389648. Assayed/reported partner: UniProtKB:Q13485. |
| GO:0005515 protein binding | IPI PMID:9702198 Characterization of human FAST-1, a TGF beta and activin sig... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:9702198. Assayed/reported partner: UniProtKB:O75593. |
| GO:0005515 protein binding | IPI PMID:9865696 SARA, a FYVE domain protein that recruits Smad2 to the TGFbe... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:9865696. Assayed/reported partner: UniProtKB:O95405. |
| GO:0005515 protein binding | IPI PMID:9892009 Roles of pathway-specific and inhibitory Smads in activin re... | REMOVE | Summary: Bare protein binding is uninformative under the project protein-binding policy. Reason: Bare protein binding is uninformative under the project protein-binding policy. Removal does not dispute the reported interaction; mechanistically specific binding and complex annotations are assessed separately. Original interaction source: PMID:9892009. Assayed/reported partner: UniProtKB:P36896. |
| GO:0005634 nucleus | EXP PMID:19289081 Nuclear export of Smad2 and Smad3 by RanBP3 facilitates term... | MODIFY | Summary: Nuclear accumulation is established; nucleoplasm and chromatin specify the supported transcriptional compartment more precisely and are already annotated. Reason: Nuclear accumulation is established; nucleoplasm and chromatin specify the supported transcriptional compartment more precisely and are already annotated. Proposed replacements: nucleoplasm chromatin Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:21828274 We identified a new motif, termed SMAD complex-associated (SCA), that is bound by SMAD2/3/4 and FOXH1 in human embryonic stem cells (hESCs) and derived endoderm. |
| GO:0005634 nucleus | EXP PMID:22781750 Protein phosphatase 5 modulates SMAD3 function in the transf... | MODIFY | Summary: Nuclear accumulation is established; nucleoplasm and chromatin specify the supported transcriptional compartment more precisely and are already annotated. Reason: Nuclear accumulation is established; nucleoplasm and chromatin specify the supported transcriptional compartment more precisely and are already annotated. Proposed replacements: nucleoplasm chromatin Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:21828274 We identified a new motif, termed SMAD complex-associated (SCA), that is bound by SMAD2/3/4 and FOXH1 in human embryonic stem cells (hESCs) and derived endoderm. |
| GO:0005634 nucleus | EXP PMID:9865696 SARA, a FYVE domain protein that recruits Smad2 to the TGFbe... | MODIFY | Summary: Nuclear accumulation is established; nucleoplasm and chromatin specify the supported transcriptional compartment more precisely and are already annotated. Reason: Nuclear accumulation is established; nucleoplasm and chromatin specify the supported transcriptional compartment more precisely and are already annotated. Proposed replacements: nucleoplasm chromatin Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:21828274 We identified a new motif, termed SMAD complex-associated (SCA), that is bound by SMAD2/3/4 and FOXH1 in human embryonic stem cells (hESCs) and derived endoderm. |
| GO:0005634 nucleus | IDA PMID:12411310 Cellular response to hypoxia involves signaling via Smad pro... | MODIFY | Summary: Nuclear accumulation is established; nucleoplasm and chromatin specify the supported transcriptional compartment more precisely and are already annotated. Reason: Nuclear accumulation is established; nucleoplasm and chromatin specify the supported transcriptional compartment more precisely and are already annotated. Proposed replacements: nucleoplasm chromatin Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:21828274 We identified a new motif, termed SMAD complex-associated (SCA), that is bound by SMAD2/3/4 and FOXH1 in human embryonic stem cells (hESCs) and derived endoderm. |
| GO:0005634 nucleus | IDA PMID:16751101 PPM1A functions as a Smad phosphatase to terminate TGFbeta s... | MODIFY | Summary: Nuclear accumulation is established; nucleoplasm and chromatin specify the supported transcriptional compartment more precisely and are already annotated. Reason: Nuclear accumulation is established; nucleoplasm and chromatin specify the supported transcriptional compartment more precisely and are already annotated. Proposed replacements: nucleoplasm chromatin Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:21828274 We identified a new motif, termed SMAD complex-associated (SCA), that is bound by SMAD2/3/4 and FOXH1 in human embryonic stem cells (hESCs) and derived endoderm. |
| GO:0005634 nucleus | IDA PMID:21145499 The Crumbs complex couples cell density sensing to Hippo-dep... | MODIFY | Summary: Nuclear accumulation is established; nucleoplasm and chromatin specify the supported transcriptional compartment more precisely and are already annotated. Reason: Nuclear accumulation is established; nucleoplasm and chromatin specify the supported transcriptional compartment more precisely and are already annotated. Proposed replacements: nucleoplasm chromatin Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:21828274 We identified a new motif, termed SMAD complex-associated (SCA), that is bound by SMAD2/3/4 and FOXH1 in human embryonic stem cells (hESCs) and derived endoderm. |
| GO:0005634 nucleus | IDA PMID:21599657 ZNF580, a novel C2H2 zinc-finger transcription factor, inter... | MODIFY | Summary: Nuclear accumulation is established; nucleoplasm and chromatin specify the supported transcriptional compartment more precisely and are already annotated. Reason: Nuclear accumulation is established; nucleoplasm and chromatin specify the supported transcriptional compartment more precisely and are already annotated. Proposed replacements: nucleoplasm chromatin Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:21828274 We identified a new motif, termed SMAD complex-associated (SCA), that is bound by SMAD2/3/4 and FOXH1 in human embryonic stem cells (hESCs) and derived endoderm. |
| GO:0005634 nucleus | IDA PMID:25893292 Syntenin regulates TGF-Ξ²1-induced Smad activation and the ep... | MODIFY | Summary: Nuclear accumulation is established; nucleoplasm and chromatin specify the supported transcriptional compartment more precisely and are already annotated. Reason: Nuclear accumulation is established; nucleoplasm and chromatin specify the supported transcriptional compartment more precisely and are already annotated. Proposed replacements: nucleoplasm chromatin Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:21828274 We identified a new motif, termed SMAD complex-associated (SCA), that is bound by SMAD2/3/4 and FOXH1 in human embryonic stem cells (hESCs) and derived endoderm. |
| GO:0005634 nucleus | IDA PMID:8980228 MADR2 is a substrate of the TGFbeta receptor and its phospho... | MODIFY | Summary: Nuclear accumulation is established; nucleoplasm and chromatin specify the supported transcriptional compartment more precisely and are already annotated. Reason: Nuclear accumulation is established; nucleoplasm and chromatin specify the supported transcriptional compartment more precisely and are already annotated. Proposed replacements: nucleoplasm chromatin Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:21828274 We identified a new motif, termed SMAD complex-associated (SCA), that is bound by SMAD2/3/4 and FOXH1 in human embryonic stem cells (hESCs) and derived endoderm. |
| GO:0005634 nucleus | IDA PMID:9311995 TGF-beta receptor-mediated signalling through Smad2, Smad3 a... | MODIFY | Summary: Nuclear accumulation is established; nucleoplasm and chromatin specify the supported transcriptional compartment more precisely and are already annotated. Reason: Nuclear accumulation is established; nucleoplasm and chromatin specify the supported transcriptional compartment more precisely and are already annotated. Proposed replacements: nucleoplasm chromatin Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:21828274 We identified a new motif, termed SMAD complex-associated (SCA), that is bound by SMAD2/3/4 and FOXH1 in human embryonic stem cells (hESCs) and derived endoderm. |
| GO:0005634 nucleus | IDA PMID:9389648 Dual role of the Smad4/DPC4 tumor suppressor in TGFbeta-indu... | MODIFY | Summary: Nuclear accumulation is established; nucleoplasm and chromatin specify the supported transcriptional compartment more precisely and are already annotated. Reason: Nuclear accumulation is established; nucleoplasm and chromatin specify the supported transcriptional compartment more precisely and are already annotated. Proposed replacements: nucleoplasm chromatin Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:21828274 We identified a new motif, termed SMAD complex-associated (SCA), that is bound by SMAD2/3/4 and FOXH1 in human embryonic stem cells (hESCs) and derived endoderm. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | MODIFY | Summary: Nuclear accumulation is established; nucleoplasm and chromatin specify the supported transcriptional compartment more precisely and are already annotated. Reason: Nuclear accumulation is established; nucleoplasm and chromatin specify the supported transcriptional compartment more precisely and are already annotated. Proposed replacements: nucleoplasm chromatin Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:21828274 We identified a new motif, termed SMAD complex-associated (SCA), that is bound by SMAD2/3/4 and FOXH1 in human embryonic stem cells (hESCs) and derived endoderm. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Reason: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0005654 nucleoplasm | IEA GO_REF:0000117 | ACCEPT | Summary: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Reason: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-1112609 | ACCEPT | Summary: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Reason: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-1535903 | ACCEPT | Summary: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Reason: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-173481 | ACCEPT | Summary: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Reason: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-173488 | ACCEPT | Summary: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Reason: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-173545 | ACCEPT | Summary: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Reason: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-209055 | ACCEPT | Summary: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Reason: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-2106579 | ACCEPT | Summary: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Reason: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-2127257 | ACCEPT | Summary: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Reason: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-2176475 | ACCEPT | Summary: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Reason: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-2176491 | ACCEPT | Summary: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Reason: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-2176502 | ACCEPT | Summary: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Reason: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-2176503 | ACCEPT | Summary: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Reason: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-2179274 | ACCEPT | Summary: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Reason: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-2179276 | ACCEPT | Summary: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Reason: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-2186607 | ACCEPT | Summary: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Reason: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-2186643 | ACCEPT | Summary: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Reason: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-2187309 | ACCEPT | Summary: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Reason: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-2187325 | ACCEPT | Summary: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Reason: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-2187330 | ACCEPT | Summary: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Reason: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-2187388 | ACCEPT | Summary: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Reason: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-2187395 | ACCEPT | Summary: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Reason: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-480204 | ACCEPT | Summary: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Reason: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-870449 | ACCEPT | Summary: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Reason: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-870538 | ACCEPT | Summary: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Reason: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9617996 | ACCEPT | Summary: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Reason: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9618004 | ACCEPT | Summary: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Reason: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9618021 | ACCEPT | Summary: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Reason: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9736959 | ACCEPT | Summary: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Reason: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9736970 | ACCEPT | Summary: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Reason: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9736979 | ACCEPT | Summary: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Reason: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9736984 | ACCEPT | Summary: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Reason: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9736992 | ACCEPT | Summary: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Reason: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9823952 | ACCEPT | Summary: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Reason: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9823959 | ACCEPT | Summary: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Reason: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0005654 nucleoplasm | TAS Reactome:R-NUL-2186736 | ACCEPT | Summary: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Reason: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0005654 nucleoplasm | TAS Reactome:R-NUL-2186755 | ACCEPT | Summary: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Reason: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0005654 nucleoplasm | TAS Reactome:R-NUL-9625758 | ACCEPT | Summary: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Reason: The nucleoplasmic pool participates in receptor-induced SMAD complex formation and target-gene regulation; nuclear transport and DNA-associated complexes independently support the compartment. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0005667 transcription regulator complex | IDA PMID:17438144 Smad7 antagonizes transforming growth factor beta signaling ... | MODIFY | Summary: The relevant transcription regulator assembly is specifically a heteromeric SMAD protein complex, already annotated. Reason: The relevant transcription regulator assembly is specifically a heteromeric SMAD protein complex, already annotated. This refinement retains the real complex-membership claim. Proposed replacements: heteromeric SMAD protein complex Supporting Evidence: PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0005667 transcription regulator complex | IEA GO_REF:0000120 | MODIFY | Summary: The relevant transcription regulator assembly is specifically a heteromeric SMAD protein complex, already annotated. Reason: The relevant transcription regulator assembly is specifically a heteromeric SMAD protein complex, already annotated. This refinement retains the real complex-membership claim. Proposed replacements: heteromeric SMAD protein complex Supporting Evidence: PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0005730 nucleolus | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Human Protein Atlas immunofluorescence independently reports supported nucleolar localization. Reason: Human Protein Atlas immunofluorescence independently reports supported nucleolar localization. Retain this cell-context localization without inferring ribosome-biogenesis activity. Supporting Evidence: file:human/SMAD2/SMAD2-notes.md Mainly localized to the nucleoplasm and nucleoli. |
| GO:0005737 cytoplasm | EXP PMID:16751101 PPM1A functions as a Smad phosphatase to terminate TGFbeta s... | MODIFY | Summary: The soluble cytoplasmic signaling pool can be specified as cytosol, already annotated, while nuclear pools are captured separately. Reason: The soluble cytoplasmic signaling pool can be specified as cytosol, already annotated, while nuclear pools are captured separately. Proposed replacements: cytosol Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. file:human/SMAD2/SMAD2-uniprot.txt Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus when complexed with SMAD4 or with IPO7 |
| GO:0005737 cytoplasm | EXP PMID:19289081 Nuclear export of Smad2 and Smad3 by RanBP3 facilitates term... | MODIFY | Summary: The soluble cytoplasmic signaling pool can be specified as cytosol, already annotated, while nuclear pools are captured separately. Reason: The soluble cytoplasmic signaling pool can be specified as cytosol, already annotated, while nuclear pools are captured separately. Proposed replacements: cytosol Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. file:human/SMAD2/SMAD2-uniprot.txt Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus when complexed with SMAD4 or with IPO7 |
| GO:0005737 cytoplasm | EXP PMID:9865696 SARA, a FYVE domain protein that recruits Smad2 to the TGFbe... | MODIFY | Summary: The soluble cytoplasmic signaling pool can be specified as cytosol, already annotated, while nuclear pools are captured separately. Reason: The soluble cytoplasmic signaling pool can be specified as cytosol, already annotated, while nuclear pools are captured separately. Proposed replacements: cytosol Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. file:human/SMAD2/SMAD2-uniprot.txt Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus when complexed with SMAD4 or with IPO7 |
| GO:0005737 cytoplasm | IDA PMID:12411310 Cellular response to hypoxia involves signaling via Smad pro... | MODIFY | Summary: The soluble cytoplasmic signaling pool can be specified as cytosol, already annotated, while nuclear pools are captured separately. Reason: The soluble cytoplasmic signaling pool can be specified as cytosol, already annotated, while nuclear pools are captured separately. Proposed replacements: cytosol Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. file:human/SMAD2/SMAD2-uniprot.txt Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus when complexed with SMAD4 or with IPO7 |
| GO:0005737 cytoplasm | IDA PMID:21145499 The Crumbs complex couples cell density sensing to Hippo-dep... | MODIFY | Summary: The soluble cytoplasmic signaling pool can be specified as cytosol, already annotated, while nuclear pools are captured separately. Reason: The soluble cytoplasmic signaling pool can be specified as cytosol, already annotated, while nuclear pools are captured separately. Proposed replacements: cytosol Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. file:human/SMAD2/SMAD2-uniprot.txt Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus when complexed with SMAD4 or with IPO7 |
| GO:0005737 cytoplasm | IDA PMID:9311995 TGF-beta receptor-mediated signalling through Smad2, Smad3 a... | MODIFY | Summary: The soluble cytoplasmic signaling pool can be specified as cytosol, already annotated, while nuclear pools are captured separately. Reason: The soluble cytoplasmic signaling pool can be specified as cytosol, already annotated, while nuclear pools are captured separately. Proposed replacements: cytosol Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. file:human/SMAD2/SMAD2-uniprot.txt Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus when complexed with SMAD4 or with IPO7 |
| GO:0005737 cytoplasm | IDA PMID:9389648 Dual role of the Smad4/DPC4 tumor suppressor in TGFbeta-indu... | MODIFY | Summary: The soluble cytoplasmic signaling pool can be specified as cytosol, already annotated, while nuclear pools are captured separately. Reason: The soluble cytoplasmic signaling pool can be specified as cytosol, already annotated, while nuclear pools are captured separately. Proposed replacements: cytosol Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. file:human/SMAD2/SMAD2-uniprot.txt Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus when complexed with SMAD4 or with IPO7 |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | MODIFY | Summary: The soluble cytoplasmic signaling pool can be specified as cytosol, already annotated, while nuclear pools are captured separately. Reason: The soluble cytoplasmic signaling pool can be specified as cytosol, already annotated, while nuclear pools are captured separately. Proposed replacements: cytosol Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. file:human/SMAD2/SMAD2-uniprot.txt Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus when complexed with SMAD4 or with IPO7 |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Cytosolic SMAD pools and ligand-regulated nuclear accumulation are integral to the signal-transduction cycle, independently supported by localization studies and curated pathway reactions. Reason: Cytosolic SMAD pools and ligand-regulated nuclear accumulation are integral to the signal-transduction cycle, independently supported by localization studies and curated pathway reactions. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. file:human/SMAD2/SMAD2-uniprot.txt Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus when complexed with SMAD4 or with IPO7 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1549526 | ACCEPT | Summary: Cytosolic SMAD pools and ligand-regulated nuclear accumulation are integral to the signal-transduction cycle, independently supported by localization studies and curated pathway reactions. Reason: Cytosolic SMAD pools and ligand-regulated nuclear accumulation are integral to the signal-transduction cycle, independently supported by localization studies and curated pathway reactions. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. file:human/SMAD2/SMAD2-uniprot.txt Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus when complexed with SMAD4 or with IPO7 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-170835 | ACCEPT | Summary: Cytosolic SMAD pools and ligand-regulated nuclear accumulation are integral to the signal-transduction cycle, independently supported by localization studies and curated pathway reactions. Reason: Cytosolic SMAD pools and ligand-regulated nuclear accumulation are integral to the signal-transduction cycle, independently supported by localization studies and curated pathway reactions. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. file:human/SMAD2/SMAD2-uniprot.txt Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus when complexed with SMAD4 or with IPO7 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-170847 | ACCEPT | Summary: Cytosolic SMAD pools and ligand-regulated nuclear accumulation are integral to the signal-transduction cycle, independently supported by localization studies and curated pathway reactions. Reason: Cytosolic SMAD pools and ligand-regulated nuclear accumulation are integral to the signal-transduction cycle, independently supported by localization studies and curated pathway reactions. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. file:human/SMAD2/SMAD2-uniprot.txt Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus when complexed with SMAD4 or with IPO7 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-170850 | ACCEPT | Summary: Cytosolic SMAD pools and ligand-regulated nuclear accumulation are integral to the signal-transduction cycle, independently supported by localization studies and curated pathway reactions. Reason: Cytosolic SMAD pools and ligand-regulated nuclear accumulation are integral to the signal-transduction cycle, independently supported by localization studies and curated pathway reactions. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. file:human/SMAD2/SMAD2-uniprot.txt Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus when complexed with SMAD4 or with IPO7 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-170868 | ACCEPT | Summary: Cytosolic SMAD pools and ligand-regulated nuclear accumulation are integral to the signal-transduction cycle, independently supported by localization studies and curated pathway reactions. Reason: Cytosolic SMAD pools and ligand-regulated nuclear accumulation are integral to the signal-transduction cycle, independently supported by localization studies and curated pathway reactions. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. file:human/SMAD2/SMAD2-uniprot.txt Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus when complexed with SMAD4 or with IPO7 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-173488 | ACCEPT | Summary: Cytosolic SMAD pools and ligand-regulated nuclear accumulation are integral to the signal-transduction cycle, independently supported by localization studies and curated pathway reactions. Reason: Cytosolic SMAD pools and ligand-regulated nuclear accumulation are integral to the signal-transduction cycle, independently supported by localization studies and curated pathway reactions. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. file:human/SMAD2/SMAD2-uniprot.txt Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus when complexed with SMAD4 or with IPO7 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-173542 | ACCEPT | Summary: Cytosolic SMAD pools and ligand-regulated nuclear accumulation are integral to the signal-transduction cycle, independently supported by localization studies and curated pathway reactions. Reason: Cytosolic SMAD pools and ligand-regulated nuclear accumulation are integral to the signal-transduction cycle, independently supported by localization studies and curated pathway reactions. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. file:human/SMAD2/SMAD2-uniprot.txt Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus when complexed with SMAD4 or with IPO7 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2031355 | ACCEPT | Summary: Cytosolic SMAD pools and ligand-regulated nuclear accumulation are integral to the signal-transduction cycle, independently supported by localization studies and curated pathway reactions. Reason: Cytosolic SMAD pools and ligand-regulated nuclear accumulation are integral to the signal-transduction cycle, independently supported by localization studies and curated pathway reactions. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. file:human/SMAD2/SMAD2-uniprot.txt Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus when complexed with SMAD4 or with IPO7 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2106579 | ACCEPT | Summary: Cytosolic SMAD pools and ligand-regulated nuclear accumulation are integral to the signal-transduction cycle, independently supported by localization studies and curated pathway reactions. Reason: Cytosolic SMAD pools and ligand-regulated nuclear accumulation are integral to the signal-transduction cycle, independently supported by localization studies and curated pathway reactions. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. file:human/SMAD2/SMAD2-uniprot.txt Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus when complexed with SMAD4 or with IPO7 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2176445 | ACCEPT | Summary: Cytosolic SMAD pools and ligand-regulated nuclear accumulation are integral to the signal-transduction cycle, independently supported by localization studies and curated pathway reactions. Reason: Cytosolic SMAD pools and ligand-regulated nuclear accumulation are integral to the signal-transduction cycle, independently supported by localization studies and curated pathway reactions. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. file:human/SMAD2/SMAD2-uniprot.txt Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus when complexed with SMAD4 or with IPO7 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2176452 | ACCEPT | Summary: Cytosolic SMAD pools and ligand-regulated nuclear accumulation are integral to the signal-transduction cycle, independently supported by localization studies and curated pathway reactions. Reason: Cytosolic SMAD pools and ligand-regulated nuclear accumulation are integral to the signal-transduction cycle, independently supported by localization studies and curated pathway reactions. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. file:human/SMAD2/SMAD2-uniprot.txt Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus when complexed with SMAD4 or with IPO7 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2187355 | ACCEPT | Summary: Cytosolic SMAD pools and ligand-regulated nuclear accumulation are integral to the signal-transduction cycle, independently supported by localization studies and curated pathway reactions. Reason: Cytosolic SMAD pools and ligand-regulated nuclear accumulation are integral to the signal-transduction cycle, independently supported by localization studies and curated pathway reactions. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. file:human/SMAD2/SMAD2-uniprot.txt Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus when complexed with SMAD4 or with IPO7 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2187358 | ACCEPT | Summary: Cytosolic SMAD pools and ligand-regulated nuclear accumulation are integral to the signal-transduction cycle, independently supported by localization studies and curated pathway reactions. Reason: Cytosolic SMAD pools and ligand-regulated nuclear accumulation are integral to the signal-transduction cycle, independently supported by localization studies and curated pathway reactions. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. file:human/SMAD2/SMAD2-uniprot.txt Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus when complexed with SMAD4 or with IPO7 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2187395 | ACCEPT | Summary: Cytosolic SMAD pools and ligand-regulated nuclear accumulation are integral to the signal-transduction cycle, independently supported by localization studies and curated pathway reactions. Reason: Cytosolic SMAD pools and ligand-regulated nuclear accumulation are integral to the signal-transduction cycle, independently supported by localization studies and curated pathway reactions. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. file:human/SMAD2/SMAD2-uniprot.txt Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus when complexed with SMAD4 or with IPO7 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2187401 | ACCEPT | Summary: Cytosolic SMAD pools and ligand-regulated nuclear accumulation are integral to the signal-transduction cycle, independently supported by localization studies and curated pathway reactions. Reason: Cytosolic SMAD pools and ligand-regulated nuclear accumulation are integral to the signal-transduction cycle, independently supported by localization studies and curated pathway reactions. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. file:human/SMAD2/SMAD2-uniprot.txt Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus when complexed with SMAD4 or with IPO7 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2187405 | ACCEPT | Summary: Cytosolic SMAD pools and ligand-regulated nuclear accumulation are integral to the signal-transduction cycle, independently supported by localization studies and curated pathway reactions. Reason: Cytosolic SMAD pools and ligand-regulated nuclear accumulation are integral to the signal-transduction cycle, independently supported by localization studies and curated pathway reactions. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. file:human/SMAD2/SMAD2-uniprot.txt Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus when complexed with SMAD4 or with IPO7 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3304394 | ACCEPT | Summary: Cytosolic SMAD pools and ligand-regulated nuclear accumulation are integral to the signal-transduction cycle, independently supported by localization studies and curated pathway reactions. Reason: Cytosolic SMAD pools and ligand-regulated nuclear accumulation are integral to the signal-transduction cycle, independently supported by localization studies and curated pathway reactions. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. file:human/SMAD2/SMAD2-uniprot.txt Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus when complexed with SMAD4 or with IPO7 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3311014 | ACCEPT | Summary: Cytosolic SMAD pools and ligand-regulated nuclear accumulation are integral to the signal-transduction cycle, independently supported by localization studies and curated pathway reactions. Reason: Cytosolic SMAD pools and ligand-regulated nuclear accumulation are integral to the signal-transduction cycle, independently supported by localization studies and curated pathway reactions. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. file:human/SMAD2/SMAD2-uniprot.txt Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus when complexed with SMAD4 or with IPO7 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3315483 | ACCEPT | Summary: Cytosolic SMAD pools and ligand-regulated nuclear accumulation are integral to the signal-transduction cycle, independently supported by localization studies and curated pathway reactions. Reason: Cytosolic SMAD pools and ligand-regulated nuclear accumulation are integral to the signal-transduction cycle, independently supported by localization studies and curated pathway reactions. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. file:human/SMAD2/SMAD2-uniprot.txt Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus when complexed with SMAD4 or with IPO7 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3656523 | ACCEPT | Summary: Cytosolic SMAD pools and ligand-regulated nuclear accumulation are integral to the signal-transduction cycle, independently supported by localization studies and curated pathway reactions. Reason: Cytosolic SMAD pools and ligand-regulated nuclear accumulation are integral to the signal-transduction cycle, independently supported by localization studies and curated pathway reactions. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. file:human/SMAD2/SMAD2-uniprot.txt Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus when complexed with SMAD4 or with IPO7 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6781764 | ACCEPT | Summary: Cytosolic SMAD pools and ligand-regulated nuclear accumulation are integral to the signal-transduction cycle, independently supported by localization studies and curated pathway reactions. Reason: Cytosolic SMAD pools and ligand-regulated nuclear accumulation are integral to the signal-transduction cycle, independently supported by localization studies and curated pathway reactions. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. file:human/SMAD2/SMAD2-uniprot.txt Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus when complexed with SMAD4 or with IPO7 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9731111 | ACCEPT | Summary: Cytosolic SMAD pools and ligand-regulated nuclear accumulation are integral to the signal-transduction cycle, independently supported by localization studies and curated pathway reactions. Reason: Cytosolic SMAD pools and ligand-regulated nuclear accumulation are integral to the signal-transduction cycle, independently supported by localization studies and curated pathway reactions. Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. file:human/SMAD2/SMAD2-uniprot.txt Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus when complexed with SMAD4 or with IPO7 |
| GO:0006351 DNA-templated transcription | NAS PMID:15350224 Structural basis of heteromeric smad protein assembly in TGF... | MODIFY | Summary: SMAD proteins regulate transcription rather than catalyzing RNA synthesis. Reason: SMAD proteins regulate transcription rather than catalyzing RNA synthesis. Refine to regulation of transcription by RNA polymerase II; no RNA polymerase activity is assigned. Proposed replacements: regulation of transcription by RNA polymerase II Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000002 | MODIFY | Summary: The supported regulated genes are transcribed by RNA polymerase II. Reason: The supported regulated genes are transcribed by RNA polymerase II. The polymerase-specific regulation term expresses this role more precisely. Proposed replacements: regulation of transcription by RNA polymerase II Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. |
| GO:0006355 regulation of DNA-templated transcription | NAS PMID:35359452 The Interplay Between TGF-Ξ² Signaling and Cell Metabolism. | MODIFY | Summary: The supported regulated genes are transcribed by RNA polymerase II. Reason: The supported regulated genes are transcribed by RNA polymerase II. The polymerase-specific regulation term expresses this role more precisely. Proposed replacements: regulation of transcription by RNA polymerase II Supporting Evidence: PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. |
| GO:0007179 transforming growth factor beta receptor signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: Core TGF-beta receptor signaling proceeds through receptor-activated R-SMADs and SMAD4-containing nuclear complexes. Reason: Core TGF-beta receptor signaling proceeds through receptor-activated R-SMADs and SMAD4-containing nuclear complexes. These proteins execute signal-dependent complex assembly and transcription, not receptor kinase catalysis. Supporting Evidence: PMID:8980228 MADR2 and not the related protein DPC4 transiently interacts with the TGFbeta receptor and is directly phosphorylated by the complex on C-terminal serines. PMID:9311995 Smads 2 and 3 interacted with Smad4 after TbetaR activation in transfected COS cells. PMID:9311995 Smads 2, 3 and 4 accumulated in the nucleus upon TGF-beta1 treatment in Mv1Lu cells, and showed a synergistic effect in a transcriptional reporter assay using the TGF-beta-inducible plasminogen activator inhibitor-1 promoter. |
| GO:0007179 transforming growth factor beta receptor signaling pathway | IDA PMID:18548003 SMAD proteins control DROSHA-mediated microRNA maturation. | ACCEPT | Summary: Core TGF-beta receptor signaling proceeds through receptor-activated R-SMADs and SMAD4-containing nuclear complexes. Reason: Core TGF-beta receptor signaling proceeds through receptor-activated R-SMADs and SMAD4-containing nuclear complexes. These proteins execute signal-dependent complex assembly and transcription, not receptor kinase catalysis. Supporting Evidence: PMID:8980228 MADR2 and not the related protein DPC4 transiently interacts with the TGFbeta receptor and is directly phosphorylated by the complex on C-terminal serines. PMID:9311995 Smads 2 and 3 interacted with Smad4 after TbetaR activation in transfected COS cells. PMID:9311995 Smads 2, 3 and 4 accumulated in the nucleus upon TGF-beta1 treatment in Mv1Lu cells, and showed a synergistic effect in a transcriptional reporter assay using the TGF-beta-inducible plasminogen activator inhibitor-1 promoter. |
| GO:0007179 transforming growth factor beta receptor signaling pathway | IDA PMID:8752209 MADR2 maps to 18q21 and encodes a TGFbeta-regulated MAD-rela... | ACCEPT | Summary: Core TGF-beta receptor signaling proceeds through receptor-activated R-SMADs and SMAD4-containing nuclear complexes. Reason: Core TGF-beta receptor signaling proceeds through receptor-activated R-SMADs and SMAD4-containing nuclear complexes. These proteins execute signal-dependent complex assembly and transcription, not receptor kinase catalysis. Supporting Evidence: PMID:8980228 MADR2 and not the related protein DPC4 transiently interacts with the TGFbeta receptor and is directly phosphorylated by the complex on C-terminal serines. PMID:9311995 Smads 2 and 3 interacted with Smad4 after TbetaR activation in transfected COS cells. PMID:9311995 Smads 2, 3 and 4 accumulated in the nucleus upon TGF-beta1 treatment in Mv1Lu cells, and showed a synergistic effect in a transcriptional reporter assay using the TGF-beta-inducible plasminogen activator inhibitor-1 promoter. |
| GO:0007179 transforming growth factor beta receptor signaling pathway | IDA PMID:9311995 TGF-beta receptor-mediated signalling through Smad2, Smad3 a... | ACCEPT | Summary: Core TGF-beta receptor signaling proceeds through receptor-activated R-SMADs and SMAD4-containing nuclear complexes. Reason: Core TGF-beta receptor signaling proceeds through receptor-activated R-SMADs and SMAD4-containing nuclear complexes. These proteins execute signal-dependent complex assembly and transcription, not receptor kinase catalysis. Supporting Evidence: PMID:8980228 MADR2 and not the related protein DPC4 transiently interacts with the TGFbeta receptor and is directly phosphorylated by the complex on C-terminal serines. PMID:9311995 Smads 2 and 3 interacted with Smad4 after TbetaR activation in transfected COS cells. PMID:9311995 Smads 2, 3 and 4 accumulated in the nucleus upon TGF-beta1 treatment in Mv1Lu cells, and showed a synergistic effect in a transcriptional reporter assay using the TGF-beta-inducible plasminogen activator inhibitor-1 promoter. |
| GO:0007179 transforming growth factor beta receptor signaling pathway | IDA PMID:9389648 Dual role of the Smad4/DPC4 tumor suppressor in TGFbeta-indu... | ACCEPT | Summary: Core TGF-beta receptor signaling proceeds through receptor-activated R-SMADs and SMAD4-containing nuclear complexes. Reason: Core TGF-beta receptor signaling proceeds through receptor-activated R-SMADs and SMAD4-containing nuclear complexes. These proteins execute signal-dependent complex assembly and transcription, not receptor kinase catalysis. Supporting Evidence: PMID:8980228 MADR2 and not the related protein DPC4 transiently interacts with the TGFbeta receptor and is directly phosphorylated by the complex on C-terminal serines. PMID:9311995 Smads 2 and 3 interacted with Smad4 after TbetaR activation in transfected COS cells. PMID:9311995 Smads 2, 3 and 4 accumulated in the nucleus upon TGF-beta1 treatment in Mv1Lu cells, and showed a synergistic effect in a transcriptional reporter assay using the TGF-beta-inducible plasminogen activator inhibitor-1 promoter. |
| GO:0007179 transforming growth factor beta receptor signaling pathway | IDA PMID:9732876 Smad3 and Smad4 cooperate with c-Jun/c-Fos to mediate TGF-be... | ACCEPT | Summary: Core TGF-beta receptor signaling proceeds through receptor-activated R-SMADs and SMAD4-containing nuclear complexes. Reason: Core TGF-beta receptor signaling proceeds through receptor-activated R-SMADs and SMAD4-containing nuclear complexes. These proteins execute signal-dependent complex assembly and transcription, not receptor kinase catalysis. Supporting Evidence: PMID:8980228 MADR2 and not the related protein DPC4 transiently interacts with the TGFbeta receptor and is directly phosphorylated by the complex on C-terminal serines. PMID:9311995 Smads 2 and 3 interacted with Smad4 after TbetaR activation in transfected COS cells. PMID:9311995 Smads 2, 3 and 4 accumulated in the nucleus upon TGF-beta1 treatment in Mv1Lu cells, and showed a synergistic effect in a transcriptional reporter assay using the TGF-beta-inducible plasminogen activator inhibitor-1 promoter. |
| GO:0007179 transforming growth factor beta receptor signaling pathway | IEA GO_REF:0000117 | ACCEPT | Summary: Core TGF-beta receptor signaling proceeds through receptor-activated R-SMADs and SMAD4-containing nuclear complexes. Reason: Core TGF-beta receptor signaling proceeds through receptor-activated R-SMADs and SMAD4-containing nuclear complexes. These proteins execute signal-dependent complex assembly and transcription, not receptor kinase catalysis. Supporting Evidence: PMID:8980228 MADR2 and not the related protein DPC4 transiently interacts with the TGFbeta receptor and is directly phosphorylated by the complex on C-terminal serines. PMID:9311995 Smads 2 and 3 interacted with Smad4 after TbetaR activation in transfected COS cells. PMID:9311995 Smads 2, 3 and 4 accumulated in the nucleus upon TGF-beta1 treatment in Mv1Lu cells, and showed a synergistic effect in a transcriptional reporter assay using the TGF-beta-inducible plasminogen activator inhibitor-1 promoter. |
| GO:0007179 transforming growth factor beta receptor signaling pathway | IMP PMID:8980228 MADR2 is a substrate of the TGFbeta receptor and its phospho... | ACCEPT | Summary: Core TGF-beta receptor signaling proceeds through receptor-activated R-SMADs and SMAD4-containing nuclear complexes. Reason: Core TGF-beta receptor signaling proceeds through receptor-activated R-SMADs and SMAD4-containing nuclear complexes. These proteins execute signal-dependent complex assembly and transcription, not receptor kinase catalysis. Supporting Evidence: PMID:8980228 MADR2 and not the related protein DPC4 transiently interacts with the TGFbeta receptor and is directly phosphorylated by the complex on C-terminal serines. PMID:9311995 Smads 2 and 3 interacted with Smad4 after TbetaR activation in transfected COS cells. PMID:9311995 Smads 2, 3 and 4 accumulated in the nucleus upon TGF-beta1 treatment in Mv1Lu cells, and showed a synergistic effect in a transcriptional reporter assay using the TGF-beta-inducible plasminogen activator inhibitor-1 promoter. |
| GO:0007179 transforming growth factor beta receptor signaling pathway | NAS PMID:35359452 The Interplay Between TGF-Ξ² Signaling and Cell Metabolism. | ACCEPT | Summary: Core TGF-beta receptor signaling proceeds through receptor-activated R-SMADs and SMAD4-containing nuclear complexes. Reason: Core TGF-beta receptor signaling proceeds through receptor-activated R-SMADs and SMAD4-containing nuclear complexes. These proteins execute signal-dependent complex assembly and transcription, not receptor kinase catalysis. Supporting Evidence: PMID:8980228 MADR2 and not the related protein DPC4 transiently interacts with the TGFbeta receptor and is directly phosphorylated by the complex on C-terminal serines. PMID:9311995 Smads 2 and 3 interacted with Smad4 after TbetaR activation in transfected COS cells. PMID:9311995 Smads 2, 3 and 4 accumulated in the nucleus upon TGF-beta1 treatment in Mv1Lu cells, and showed a synergistic effect in a transcriptional reporter assay using the TGF-beta-inducible plasminogen activator inhibitor-1 promoter. |
| GO:0007352 zygotic specification of dorsal/ventral axis | IMP PMID:9436979 Smad6 inhibits BMP/Smad1 signaling by specifically competing... | KEEP AS NON CORE | Summary: The full cited Xenopus embryo study includes SMAD2 overexpression and secondary-axis induction as an experimental comparator. Reason: The full cited Xenopus embryo study includes SMAD2 overexpression and secondary-axis induction as an experimental comparator. Retain the demonstrated dorsal/ventral developmental role with its heterologous embryo context. Supporting Evidence: PMID:9436979 Overexpression of Smad2 has the same effect [Fig. |
| GO:0007369 gastrulation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: SMAD2 mediates Nodal-dependent mesendoderm allocation during gastrulation; conditional epiblast loss need not abolish gastrulation movements, so participation is not equated with sole control of the process. Reason: SMAD2 mediates Nodal-dependent mesendoderm allocation during gastrulation; conditional epiblast loss need not abolish gastrulation movements, so participation is not equated with sole control of the process. Supporting Evidence: PMID:15084457 selective removal of both Smad2 and Smad3 from the epiblast additionally disrupts specification of axial and paraxial mesodermal derivatives. PMID:12842913 graded Nodal/Smad2 signals govern allocation of the axial mesendoderm precursors that selectively give rise to the ADE and PCP mesoderm. |
| GO:0007369 gastrulation | TAS PMID:19018011 Holding their own: the noncanonical roles of Smad proteins. | KEEP AS NON CORE | Summary: SMAD2 mediates Nodal-dependent mesendoderm allocation during gastrulation; conditional epiblast loss need not abolish gastrulation movements, so participation is not equated with sole control of the process. Reason: SMAD2 mediates Nodal-dependent mesendoderm allocation during gastrulation; conditional epiblast loss need not abolish gastrulation movements, so participation is not equated with sole control of the process. Supporting Evidence: PMID:15084457 selective removal of both Smad2 and Smad3 from the epiblast additionally disrupts specification of axial and paraxial mesodermal derivatives. PMID:12842913 graded Nodal/Smad2 signals govern allocation of the axial mesendoderm precursors that selectively give rise to the ADE and PCP mesoderm. |
| GO:0007498 mesoderm development | IEA GO_REF:0000117 | MODIFY | Summary: The more specific mesoderm formation process already present captures the demonstrated developmental role. Reason: The more specific mesoderm formation process already present captures the demonstrated developmental role. Proposed replacements: mesoderm formation Supporting Evidence: PMID:12842913 graded Nodal/Smad2 signals govern allocation of the axial mesendoderm precursors that selectively give rise to the ADE and PCP mesoderm. |
| GO:0009653 anatomical structure morphogenesis | IBA GO_REF:0000033 | TOO GENERAL | Summary: Morphogenesis is true but already entailed by accepted tissue-specific developmental annotations, including semilunar valve and paraxial mesoderm morphogenesis. Reason: Morphogenesis is true but already entailed by accepted tissue-specific developmental annotations, including semilunar valve and paraxial mesoderm morphogenesis. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000344419 SUPPORTS TRANSFER The ancestral assertion of anatomical structure morphogenesis is biologically defensible; target-specific evidence permits greater specificity. This is not a challenge to PAINT node placement or donor count. Supporting Evidence: PMID:23531444 faulty versican clearance due to ADAMTS5 deficiency blocks the initiation of pSmad2 signaling, which is required for excavation of endocardial cushions during aortic and pulmonary valve development. PMID:12842913 graded Nodal/Smad2 signals govern allocation of the axial mesendoderm precursors that selectively give rise to the ADE and PCP mesoderm. |
| GO:0009880 embryonic pattern specification | IEA GO_REF:0000117 | MODIFY | Summary: The broad patterning claim is supported by specific anterior/posterior patterning and organizer lineage allocation. Reason: The broad patterning claim is supported by specific anterior/posterior patterning and organizer lineage allocation. Refine to anterior/posterior pattern specification already present. Proposed replacements: anterior/posterior pattern specification Supporting Evidence: PMID:12842913 graded Nodal/Smad2 signals govern allocation of the axial mesendoderm precursors that selectively give rise to the ADE and PCP mesoderm. |
| GO:0009952 anterior/posterior pattern specification | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Conditional mouse Smad2 loss alters anterior definitive endoderm and prechordal mesoderm allocation; these are conserved but developmental-context-specific outcomes. Reason: Conditional mouse Smad2 loss alters anterior definitive endoderm and prechordal mesoderm allocation; these are conserved but developmental-context-specific outcomes. Supporting Evidence: PMID:12842913 graded Nodal/Smad2 signals govern allocation of the axial mesendoderm precursors that selectively give rise to the ADE and PCP mesoderm. |
| GO:0010629 negative regulation of gene expression | IEA GO_REF:0000117 | MODIFY | Summary: SMAD2-dependent gene repression is context-specific and acts at transcription. Reason: SMAD2-dependent gene repression is context-specific and acts at transcription. Refine to negative regulation of transcription by RNA polymerase II, without turning every SMAD response into repression. Proposed replacements: negative regulation of transcription by RNA polymerase II Supporting Evidence: PMID:14555988 we identified TGF-beta-dependent genes that are differentially regulated by Smad2 and Smad3 under regular growth conditions on a genome-wide scale. |
| GO:0010718 positive regulation of epithelial to mesenchymal transition | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SMAD complexes promote epithelial-to-mesenchymal transition through context-dependent target transcription; palatal and epithelial cell experiments support this as a specific physiological output rather than a universal outcome of all TGF-beta signaling. Reason: SMAD complexes promote epithelial-to-mesenchymal transition through context-dependent target transcription; palatal and epithelial cell experiments support this as a specific physiological output rather than a universal outcome of all TGF-beta signaling. Supporting Evidence: PMID:14691138 Our paper is the first to show that the Smad2,4/LEF1 complex replaces beta-catenin/LEF1 during activation of EMT in vivo by TGFbeta3. |
| GO:0010718 positive regulation of epithelial to mesenchymal transition | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SMAD complexes promote epithelial-to-mesenchymal transition through context-dependent target transcription; palatal and epithelial cell experiments support this as a specific physiological output rather than a universal outcome of all TGF-beta signaling. Reason: SMAD complexes promote epithelial-to-mesenchymal transition through context-dependent target transcription; palatal and epithelial cell experiments support this as a specific physiological output rather than a universal outcome of all TGF-beta signaling. Supporting Evidence: PMID:14691138 Our paper is the first to show that the Smad2,4/LEF1 complex replaces beta-catenin/LEF1 during activation of EMT in vivo by TGFbeta3. |
| GO:0017015 regulation of transforming growth factor beta receptor signaling pathway | IMP PMID:14555988 Differential regulation of TGF-beta signaling through Smad2,... | ACCEPT | Summary: SMAD2 contributes to the regulation and execution of TGF-beta-responsive gene programs. Reason: SMAD2 contributes to the regulation and execution of TGF-beta-responsive gene programs. Comparative depletion demonstrates distinct positive and negative responses rather than a uniform regulatory sign. Supporting Evidence: PMID:14555988 we identified TGF-beta-dependent genes that are differentially regulated by Smad2 and Smad3 under regular growth conditions on a genome-wide scale. |
| GO:0019902 phosphatase binding | IPI PMID:16751101 PPM1A functions as a Smad phosphatase to terminate TGFbeta s... | KEEP AS NON CORE | Summary: Binding to the phosphatase PPM1A supports termination of receptor-induced SMAD2 signaling by dephosphorylation and nuclear export. Reason: Binding to the phosphatase PPM1A supports termination of receptor-induced SMAD2 signaling by dephosphorylation and nuclear export. This is not phosphatase catalysis by SMAD2. Supporting Evidence: PMID:16751101 PPM1A dephosphorylates and promotes nuclear export of TGFbeta-activated Smad2/3. |
| GO:0030154 cell differentiation | IBA GO_REF:0000033 | TOO GENERAL | Summary: Cell differentiation is supported, but the existing odontoblast differentiation and mesoderm lineage annotations provide the informative biological contexts. Reason: Cell differentiation is supported, but the existing odontoblast differentiation and mesoderm lineage annotations provide the informative biological contexts. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000344419 SUPPORTS TRANSFER The ancestral assertion of cell differentiation is biologically defensible; target-specific evidence permits greater specificity. This is not a challenge to PAINT node placement or donor count. Supporting Evidence: PMID:33548622 IPO7 could bind to P-SMAD2 and affect the nuclear-cytoplasm-shuttling of P-SMAD2. PMID:12842913 graded Nodal/Smad2 signals govern allocation of the axial mesendoderm precursors that selectively give rise to the ADE and PCP mesoderm. |
| GO:0030279 negative regulation of ossification | IDA PMID:22155034 Bone morphogenetic protein-3b (BMP-3b) inhibits osteoblast d... | KEEP AS NON CORE | Summary: BMP3b/GDF10 activates Smad2/3 while antagonizing osteoblastic differentiation in mouse C2C12 cells. Reason: BMP3b/GDF10 activates Smad2/3 while antagonizing osteoblastic differentiation in mouse C2C12 cells. Retain the contextual anti-osteogenic output without treating SMAD2 as a canonical BMP1/5/8 branch effector. Supporting Evidence: PMID:22155034 BMP-3b suppressed the expression of osteoblastic markers including Runx2, osteocalcin and type-1 collagen induced by BMP-2, -4, -6 and -7. |
| GO:0030513 positive regulation of BMP signaling pathway | IMP PMID:19366699 Bone morphogenetic protein (BMP) and activin type II recepto... | KEEP AS NON CORE | Summary: Human pulmonary artery endothelial experiments directly show BMP9-dependent Smad2 signaling and Smad2-dependent IL-8/E-selectin transcription. Reason: Human pulmonary artery endothelial experiments directly show BMP9-dependent Smad2 signaling and Smad2-dependent IL-8/E-selectin transcription. This noncanonical vascular context prevents blanket rejection based on the usual TGF-beta/activin branch assignment. Supporting Evidence: PMID:19366699 The IL-8 and E-selectin transcriptional responses were shown to be Smad2-dependent, a novel finding. |
| GO:0031053 primary miRNA processing | TAS PMID:19018011 Holding their own: the noncanonical roles of Smad proteins. | KEEP AS NON CORE | Summary: The full primary study directly assays SMAD2: TGF-beta stimulates association of tagged SMAD2 with pri-miR-21 in COS7 RNA-ChIP experiments. Reason: The full primary study directly assays SMAD2: TGF-beta stimulates association of tagged SMAD2 with pri-miR-21 in COS7 RNA-ChIP experiments. R-SMAD recruitment to the DROSHA processing complex promotes pri-miRNA cropping. Retain the experimentally supported regulatory processing role without assigning nuclease catalysis or extending it to SMAD4. Supporting Evidence: PMID:18548003 whereas TGF-Ξ² increased binding to pri-miR-21 by SMAD2 and SMAD3, but not by SMAD1, indicating that the association between R-SMADs and pri-miR-21 is specifically regulated by ligand stimulation |
| GO:0031625 ubiquitin protein ligase binding | IPI PMID:19122240 Pin1 down-regulates transforming growth factor-beta (TGF-bet... | KEEP AS NON CORE | Summary: SMURF2 binding links SMAD2 phosphorylation state to ubiquitination and signal attenuation; no ubiquitin-ligase activity is assigned to SMAD2. Reason: SMURF2 binding links SMAD2 phosphorylation state to ubiquitination and signal attenuation; no ubiquitin-ligase activity is assigned to SMAD2. Supporting Evidence: PMID:19122240 (S/T)P motif phosphorylation also enhanced the interaction of Smad2/3 with Smurf2. |
| GO:0032444 activin responsive factor complex | IDA PMID:9389648 Dual role of the Smad4/DPC4 tumor suppressor in TGFbeta-indu... | ACCEPT | Summary: The activin-responsive FOXH1/FAST-1-SMAD2-SMAD4 transcriptional complex is specifically demonstrated. Reason: The activin-responsive FOXH1/FAST-1-SMAD2-SMAD4 transcriptional complex is specifically demonstrated. Supporting Evidence: PMID:9702198 hFAST-1 shared with xFAST-1 the ability to bind to human Smad2 and activate an activin response element (ARE). PMID:9702198 The hFAST-1-dependent activation of ARE was completely dependent on endogenous Smad4 and stimulation by a TGF beta-like ligand. PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0032924 activin receptor signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: Activin receptor signaling uses SMAD2/3 with SMAD4 and FOXH1. Reason: Activin receptor signaling uses SMAD2/3 with SMAD4 and FOXH1. Direct human FAST-1/SMAD reporter experiments independently establish the claim; Nodal-focused sources are not treated as the sole evidence for activin. Supporting Evidence: PMID:9702198 hFAST-1 shared with xFAST-1 the ability to bind to human Smad2 and activate an activin response element (ARE). PMID:9702198 The hFAST-1-dependent activation of ARE was completely dependent on endogenous Smad4 and stimulation by a TGF beta-like ligand. |
| GO:0032924 activin receptor signaling pathway | IMP PMID:15150278 Nodal and ALK7 inhibit proliferation and induce apoptosis in... | ACCEPT | Summary: Activin receptor signaling uses SMAD2/3 with SMAD4 and FOXH1. Reason: Activin receptor signaling uses SMAD2/3 with SMAD4 and FOXH1. Direct human FAST-1/SMAD reporter experiments independently establish the claim; Nodal-focused sources are not treated as the sole evidence for activin. Supporting Evidence: PMID:9702198 hFAST-1 shared with xFAST-1 the ability to bind to human Smad2 and activate an activin response element (ARE). PMID:9702198 The hFAST-1-dependent activation of ARE was completely dependent on endogenous Smad4 and stimulation by a TGF beta-like ligand. |
| GO:0032924 activin receptor signaling pathway | NAS PMID:15150278 Nodal and ALK7 inhibit proliferation and induce apoptosis in... | ACCEPT | Summary: Activin receptor signaling uses SMAD2/3 with SMAD4 and FOXH1. Reason: Activin receptor signaling uses SMAD2/3 with SMAD4 and FOXH1. Direct human FAST-1/SMAD reporter experiments independently establish the claim; Nodal-focused sources are not treated as the sole evidence for activin. Supporting Evidence: PMID:9702198 hFAST-1 shared with xFAST-1 the ability to bind to human Smad2 and activate an activin response element (ARE). PMID:9702198 The hFAST-1-dependent activation of ARE was completely dependent on endogenous Smad4 and stimulation by a TGF beta-like ligand. |
| GO:0032924 activin receptor signaling pathway | NAS PMID:15350224 Structural basis of heteromeric smad protein assembly in TGF... | ACCEPT | Summary: Activin receptor signaling uses SMAD2/3 with SMAD4 and FOXH1. Reason: Activin receptor signaling uses SMAD2/3 with SMAD4 and FOXH1. Direct human FAST-1/SMAD reporter experiments independently establish the claim; Nodal-focused sources are not treated as the sole evidence for activin. Supporting Evidence: PMID:9702198 hFAST-1 shared with xFAST-1 the ability to bind to human Smad2 and activate an activin response element (ARE). PMID:9702198 The hFAST-1-dependent activation of ARE was completely dependent on endogenous Smad4 and stimulation by a TGF beta-like ligand. |
| GO:0032991 protein-containing complex | IMP PMID:15231848 Disorder in a target for the smad2 mad homology 2 domain and... | MODIFY | Summary: The broad complex annotation is true, but heteromeric SMAD complexes are directly established and already annotated. Reason: The broad complex annotation is true, but heteromeric SMAD complexes are directly established and already annotated. Other transient interactions need not be represented as generic complex membership. Proposed replacements: heteromeric SMAD protein complex Supporting Evidence: PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0034713 type I transforming growth factor beta receptor binding | IPI PMID:8980228 MADR2 is a substrate of the TGFbeta receptor and its phospho... | ACCEPT | Summary: Transient docking to activated type I receptor permits C-terminal phosphorylation and subsequent nuclear signaling. Reason: Transient docking to activated type I receptor permits C-terminal phosphorylation and subsequent nuclear signaling. Supporting Evidence: PMID:8980228 MADR2 and not the related protein DPC4 transiently interacts with the TGFbeta receptor and is directly phosphorylated by the complex on C-terminal serines. |
| GO:0035556 intracellular signal transduction | ISS GO_REF:0000024 | MODIFY | Summary: The intracellular signaling role is specifically SMAD protein signal transduction, already annotated; these are transcriptional signal mediators, not catalytic kinases. Reason: The intracellular signaling role is specifically SMAD protein signal transduction, already annotated; these are transcriptional signal mediators, not catalytic kinases. Proposed replacements: SMAD protein signal transduction Supporting Evidence: PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. |
| GO:0038092 nodal signaling pathway | IMP PMID:15150278 Nodal and ALK7 inhibit proliferation and induce apoptosis in... | ACCEPT | Summary: Nodal signaling through ALK7 and SMAD2/3 is directly functional in human trophoblast cells, and structural/developmental work supports SMAD2 as a signal-dependent Nodal transcription factor. Reason: Nodal signaling through ALK7 and SMAD2/3 is directly functional in human trophoblast cells, and structural/developmental work supports SMAD2 as a signal-dependent Nodal transcription factor. Supporting Evidence: PMID:15150278 Nodal, acting through ALK7 and Smad2/3, inhibits proliferation and induces apoptosis in human trophoblast cells. PMID:31582430 TGF-Ξ², Nodal, and Activin receptors phosphorylate SMAD2 and SMAD3. |
| GO:0038092 nodal signaling pathway | IMP PMID:17239842 The left-right axis is regulated by the interplay of Coco, X... | ACCEPT | Summary: Nodal signaling through ALK7 and SMAD2/3 is directly functional in human trophoblast cells, and structural/developmental work supports SMAD2 as a signal-dependent Nodal transcription factor. Reason: Nodal signaling through ALK7 and SMAD2/3 is directly functional in human trophoblast cells, and structural/developmental work supports SMAD2 as a signal-dependent Nodal transcription factor. Supporting Evidence: PMID:15150278 Nodal, acting through ALK7 and Smad2/3, inhibits proliferation and induces apoptosis in human trophoblast cells. PMID:31582430 TGF-Ξ², Nodal, and Activin receptors phosphorylate SMAD2 and SMAD3. |
| GO:0042802 identical protein binding | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Self-association is structurally supported, but the main receptor-coupled transcriptional output uses R-SMAD/co-SMAD heteromers. Reason: Self-association is structurally supported, but the main receptor-coupled transcriptional output uses R-SMAD/co-SMAD heteromers. Retain genuine self-binding without treating a crystallographic homomer as the universal active species. Supporting Evidence: PMID:11779503 The crystal structure of a phosphorylated Smad2, at 1.8 A resolution, reveals the formation of a homotrimer mediated by the C-terminal phosphoserine (pSer) residues. |
| GO:0042802 identical protein binding | IPI PMID:11779503 Crystal structure of a phosphorylated Smad2. Recognition of ... | KEEP AS NON CORE | Summary: Self-association is structurally supported, but the main receptor-coupled transcriptional output uses R-SMAD/co-SMAD heteromers. Reason: Self-association is structurally supported, but the main receptor-coupled transcriptional output uses R-SMAD/co-SMAD heteromers. Retain genuine self-binding without treating a crystallographic homomer as the universal active species. Supporting Evidence: PMID:11779503 The crystal structure of a phosphorylated Smad2, at 1.8 A resolution, reveals the formation of a homotrimer mediated by the C-terminal phosphoserine (pSer) residues. |
| GO:0045165 cell fate commitment | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Conditional mouse Smad2 loss alters anterior definitive endoderm and prechordal mesoderm allocation; these are conserved but developmental-context-specific outcomes. Reason: Conditional mouse Smad2 loss alters anterior definitive endoderm and prechordal mesoderm allocation; these are conserved but developmental-context-specific outcomes. Supporting Evidence: PMID:12842913 graded Nodal/Smad2 signals govern allocation of the axial mesendoderm precursors that selectively give rise to the ADE and PCP mesoderm. |
| GO:0045596 negative regulation of cell differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SMAD2 maintains the undifferentiated primed pluripotent state in human embryonic and mouse epiblast stem cells. Reason: SMAD2 sustains Nanog and represses autocrine BMP signaling in human embryonic and mouse epiblast stem cells; its downregulation induces differentiation. This directly supports negative regulation of differentiation in a defined stem-cell context, alongside its positive developmental differentiation roles in other contexts. Supporting Evidence: PMID:23649632 We found that Smad2, but not Smad3, is required to maintain the undifferentiated pluripotent state. |
| GO:0045892 negative regulation of DNA-templated transcription | IMP PMID:14555988 Differential regulation of TGF-beta signaling through Smad2,... | MODIFY | Summary: SMAD2-dependent gene repression is context-specific and acts at transcription. Reason: SMAD2-dependent gene repression is context-specific and acts at transcription. Refine to negative regulation of transcription by RNA polymerase II, without turning every SMAD response into repression. Proposed replacements: negative regulation of transcription by RNA polymerase II Supporting Evidence: PMID:14555988 we identified TGF-beta-dependent genes that are differentially regulated by Smad2 and Smad3 under regular growth conditions on a genome-wide scale. |
| GO:0045893 positive regulation of DNA-templated transcription | IDA PMID:9311995 TGF-beta receptor-mediated signalling through Smad2, Smad3 a... | MODIFY | Summary: Positive transcriptional regulation is specifically through RNA polymerase II target genes, already represented by GO:0045944. Reason: Positive transcriptional regulation is specifically through RNA polymerase II target genes, already represented by GO:0045944. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: PMID:9311995 Smads 2, 3 and 4 accumulated in the nucleus upon TGF-beta1 treatment in Mv1Lu cells, and showed a synergistic effect in a transcriptional reporter assay using the TGF-beta-inducible plasminogen activator inhibitor-1 promoter. |
| GO:0045893 positive regulation of DNA-templated transcription | IDA PMID:9389648 Dual role of the Smad4/DPC4 tumor suppressor in TGFbeta-indu... | MODIFY | Summary: Positive transcriptional regulation is specifically through RNA polymerase II target genes, already represented by GO:0045944. Reason: Positive transcriptional regulation is specifically through RNA polymerase II target genes, already represented by GO:0045944. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: PMID:9311995 Smads 2, 3 and 4 accumulated in the nucleus upon TGF-beta1 treatment in Mv1Lu cells, and showed a synergistic effect in a transcriptional reporter assay using the TGF-beta-inducible plasminogen activator inhibitor-1 promoter. |
| GO:0045893 positive regulation of DNA-templated transcription | IDA PMID:9732876 Smad3 and Smad4 cooperate with c-Jun/c-Fos to mediate TGF-be... | MODIFY | Summary: Positive transcriptional regulation is specifically through RNA polymerase II target genes, already represented by GO:0045944. Reason: Positive transcriptional regulation is specifically through RNA polymerase II target genes, already represented by GO:0045944. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: PMID:9311995 Smads 2, 3 and 4 accumulated in the nucleus upon TGF-beta1 treatment in Mv1Lu cells, and showed a synergistic effect in a transcriptional reporter assay using the TGF-beta-inducible plasminogen activator inhibitor-1 promoter. |
| GO:0045893 positive regulation of DNA-templated transcription | IMP PMID:14555988 Differential regulation of TGF-beta signaling through Smad2,... | MODIFY | Summary: Positive transcriptional regulation is specifically through RNA polymerase II target genes, already represented by GO:0045944. Reason: Positive transcriptional regulation is specifically through RNA polymerase II target genes, already represented by GO:0045944. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: PMID:9311995 Smads 2, 3 and 4 accumulated in the nucleus upon TGF-beta1 treatment in Mv1Lu cells, and showed a synergistic effect in a transcriptional reporter assay using the TGF-beta-inducible plasminogen activator inhibitor-1 promoter. |
| GO:0045893 positive regulation of DNA-templated transcription | ISS GO_REF:0000024 | MODIFY | Summary: Positive transcriptional regulation is specifically through RNA polymerase II target genes, already represented by GO:0045944. Reason: Positive transcriptional regulation is specifically through RNA polymerase II target genes, already represented by GO:0045944. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: PMID:9311995 Smads 2, 3 and 4 accumulated in the nucleus upon TGF-beta1 treatment in Mv1Lu cells, and showed a synergistic effect in a transcriptional reporter assay using the TGF-beta-inducible plasminogen activator inhibitor-1 promoter. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: Activation of target-gene transcription is directly supported by reporter and endogenous transcription studies. Reason: Activation of target-gene transcription is directly supported by reporter and endogenous transcription studies. Coactivators and cell context determine the response. Supporting Evidence: PMID:9311995 Smads 2, 3 and 4 accumulated in the nucleus upon TGF-beta1 treatment in Mv1Lu cells, and showed a synergistic effect in a transcriptional reporter assay using the TGF-beta-inducible plasminogen activator inhibitor-1 promoter. PMID:9707553 Hetero-oligomerization of Smad4 with the pathway-restricted SMAD proteins is essential for Smad4-mediated transcription. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:9389648 Dual role of the Smad4/DPC4 tumor suppressor in TGFbeta-indu... | ACCEPT | Summary: Activation of target-gene transcription is directly supported by reporter and endogenous transcription studies. Reason: Activation of target-gene transcription is directly supported by reporter and endogenous transcription studies. Coactivators and cell context determine the response. Supporting Evidence: PMID:9311995 Smads 2, 3 and 4 accumulated in the nucleus upon TGF-beta1 treatment in Mv1Lu cells, and showed a synergistic effect in a transcriptional reporter assay using the TGF-beta-inducible plasminogen activator inhibitor-1 promoter. PMID:9707553 Hetero-oligomerization of Smad4 with the pathway-restricted SMAD proteins is essential for Smad4-mediated transcription. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | ISS GO_REF:0000024 | ACCEPT | Summary: Activation of target-gene transcription is directly supported by reporter and endogenous transcription studies. Reason: Activation of target-gene transcription is directly supported by reporter and endogenous transcription studies. Coactivators and cell context determine the response. Supporting Evidence: PMID:9311995 Smads 2, 3 and 4 accumulated in the nucleus upon TGF-beta1 treatment in Mv1Lu cells, and showed a synergistic effect in a transcriptional reporter assay using the TGF-beta-inducible plasminogen activator inhibitor-1 promoter. PMID:9707553 Hetero-oligomerization of Smad4 with the pathway-restricted SMAD proteins is essential for Smad4-mediated transcription. |
| GO:0046332 SMAD binding | IEA GO_REF:0000120 | MODIFY | Summary: SMAD2 binds co-SMAD4, other R-SMADs and inhibitory SMAD6; replace the broad family-binding term with the specific binding classes already annotated. Reason: SMAD2 binds co-SMAD4, other R-SMADs and inhibitory SMAD6; replace the broad family-binding term with the specific binding classes already annotated. The MEF2-focused source is not used as sole evidence for SMAD binding. Supporting Evidence: PMID:9311995 Smads 2 and 3 interacted with Smad4 after TbetaR activation in transfected COS cells. PMID:9311995 we observed TbetaR-activation-dependent interaction between Smad2 and Smad3. |
| GO:0046332 SMAD binding | IPI PMID:11160896 Smad proteins function as co-modulators for MEF2 transcripti... | MODIFY | Summary: SMAD2 binds co-SMAD4, other R-SMADs and inhibitory SMAD6; replace the broad family-binding term with the specific binding classes already annotated. Reason: SMAD2 binds co-SMAD4, other R-SMADs and inhibitory SMAD6; replace the broad family-binding term with the specific binding classes already annotated. The MEF2-focused source is not used as sole evidence for SMAD binding. Supporting Evidence: PMID:9311995 Smads 2 and 3 interacted with Smad4 after TbetaR activation in transfected COS cells. PMID:9311995 we observed TbetaR-activation-dependent interaction between Smad2 and Smad3. |
| GO:0048156 tau protein binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Phosphorylated-tau association is experimentally described in an Alzheimer disease/neuronal context under PIN1 regulation; it is peripheral to receptor-SMAD transcriptional signaling. Reason: Phosphorylated-tau association is experimentally described in an Alzheimer disease/neuronal context under PIN1 regulation; it is peripheral to receptor-SMAD transcriptional signaling. Supporting Evidence: PMID:24964035 Pin1 does not only affect Smad phosphorylation and stability but also regulates subcellular localization of Smad2 and supports its binding to phosphorylated tau protein. |
| GO:0048156 tau protein binding | ISS PMID:24964035 Pin1 promotes degradation of Smad proteins and their interac... | KEEP AS NON CORE | Summary: Phosphorylated-tau association is experimentally described in an Alzheimer disease/neuronal context under PIN1 regulation; it is peripheral to receptor-SMAD transcriptional signaling. Reason: Phosphorylated-tau association is experimentally described in an Alzheimer disease/neuronal context under PIN1 regulation; it is peripheral to receptor-SMAD transcriptional signaling. Supporting Evidence: PMID:24964035 Pin1 does not only affect Smad phosphorylation and stability but also regulates subcellular localization of Smad2 and supports its binding to phosphorylated tau protein. |
| GO:0048340 paraxial mesoderm morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Mesoderm formation and patterning are specific developmental outputs of Nodal/SMAD2 transcription; distinguish lineage allocation from an assertion that SMAD2 mechanically builds the tissue. Reason: Mesoderm formation and patterning are specific developmental outputs of Nodal/SMAD2 transcription; distinguish lineage allocation from an assertion that SMAD2 mechanically builds the tissue. Supporting Evidence: PMID:15084457 selective removal of both Smad2 and Smad3 from the epiblast additionally disrupts specification of axial and paraxial mesodermal derivatives. PMID:12842913 graded Nodal/Smad2 signals govern allocation of the axial mesendoderm precursors that selectively give rise to the ADE and PCP mesoderm. |
| GO:0051239 regulation of multicellular organismal process | IEA GO_REF:0000117 | TOO GENERAL | Summary: Regulation of multicellular processes is true but adds no specificity beyond the supported developmental and signaling processes. Reason: Regulation of multicellular processes is true but adds no specificity beyond the supported developmental and signaling processes. Supporting Evidence: PMID:12842913 graded Nodal/Smad2 signals govern allocation of the axial mesendoderm precursors that selectively give rise to the ADE and PCP mesoderm. |
| GO:0060395 SMAD protein signal transduction | IBA GO_REF:0000033 | ACCEPT | Summary: SMAD-mediated signal transduction is the central conserved biological role, involving phospho-dependent oligomerization, nuclear accumulation and transcriptional output. Reason: SMAD-mediated signal transduction is the central conserved biological role, involving phospho-dependent oligomerization, nuclear accumulation and transcriptional output. Supporting Evidence: PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. |
| GO:0060395 SMAD protein signal transduction | IDA PMID:16806156 Epithelial and ectomesenchymal role of the type I TGF-beta r... | ACCEPT | Summary: SMAD-mediated signal transduction is the central conserved biological role, involving phospho-dependent oligomerization, nuclear accumulation and transcriptional output. Reason: SMAD-mediated signal transduction is the central conserved biological role, involving phospho-dependent oligomerization, nuclear accumulation and transcriptional output. Supporting Evidence: PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. |
| GO:0060395 SMAD protein signal transduction | IDA PMID:9111321 Heteromeric and homomeric interactions correlate with signal... | ACCEPT | Summary: SMAD-mediated signal transduction is the central conserved biological role, involving phospho-dependent oligomerization, nuclear accumulation and transcriptional output. Reason: SMAD-mediated signal transduction is the central conserved biological role, involving phospho-dependent oligomerization, nuclear accumulation and transcriptional output. Supporting Evidence: PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. |
| GO:0060395 SMAD protein signal transduction | IDA PMID:9311995 TGF-beta receptor-mediated signalling through Smad2, Smad3 a... | ACCEPT | Summary: SMAD-mediated signal transduction is the central conserved biological role, involving phospho-dependent oligomerization, nuclear accumulation and transcriptional output. Reason: SMAD-mediated signal transduction is the central conserved biological role, involving phospho-dependent oligomerization, nuclear accumulation and transcriptional output. Supporting Evidence: PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. |
| GO:0060395 SMAD protein signal transduction | IDA PMID:9732876 Smad3 and Smad4 cooperate with c-Jun/c-Fos to mediate TGF-be... | ACCEPT | Summary: SMAD-mediated signal transduction is the central conserved biological role, involving phospho-dependent oligomerization, nuclear accumulation and transcriptional output. Reason: SMAD-mediated signal transduction is the central conserved biological role, involving phospho-dependent oligomerization, nuclear accumulation and transcriptional output. Supporting Evidence: PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. |
| GO:0060395 SMAD protein signal transduction | IEA GO_REF:0000117 | ACCEPT | Summary: SMAD-mediated signal transduction is the central conserved biological role, involving phospho-dependent oligomerization, nuclear accumulation and transcriptional output. Reason: SMAD-mediated signal transduction is the central conserved biological role, involving phospho-dependent oligomerization, nuclear accumulation and transcriptional output. Supporting Evidence: PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. |
| GO:0060395 SMAD protein signal transduction | IMP PMID:17239842 The left-right axis is regulated by the interplay of Coco, X... | ACCEPT | Summary: SMAD-mediated signal transduction is the central conserved biological role, involving phospho-dependent oligomerization, nuclear accumulation and transcriptional output. Reason: SMAD-mediated signal transduction is the central conserved biological role, involving phospho-dependent oligomerization, nuclear accumulation and transcriptional output. Supporting Evidence: PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. PMID:31582430 Thus activated, SMAD2 and SMAD3 form complexes with SMAD4, accumulate in the nucleus, and recruit coactivators and repressors to regulate the expression of target genes. |
| GO:0060485 mesenchyme development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: SMAD2 signaling contributes to development and remodeling of prevalvular mesenchyme. Reason: Mouse genetic experiments in PMID:23531444 link reduced Smad2 signaling to defective remodeling of prevalvular mesenchyme and malformed semilunar valves. This supports a conserved developmental role, with the human assignment relying on orthology rather than a direct human experiment. Mesenchyme development is as specific as this combined tissue-development evidence warrants; the valve and mesoderm morphogenesis annotations do not entail it. Retain this tissue-specific outcome as non-core relative to SMAD2 receptor-coupled transcriptional signaling. Supporting Evidence: PMID:23531444 ADAMTS5 deficient prevalvular mesenchyme also exhibited a reduction of Ξ±-smooth muscle actin and filamin A suggesting versican cleavage may be involved in TGFΞ² signaling. PMID:23531444 The Adamts5(-/-);Smad2(+/-) mice had highly penetrant BAV and bicuspid pulmonary valve (BPV) malformations as well as increased cusp and hinge size compared to the Adamts5(-/-) and control littermates. |
| GO:0061450 trophoblast cell migration | IDA PMID:34432647 GDF-8 stimulates trophoblast cell invasion by inducing ALK5-... | KEEP AS NON CORE | Summary: GDF8-dependent ALK5-SMAD2/3 induction of MMP2 supports the trophoblast invasion/migration phenotype in HTR-8/SVneo cells. Reason: GDF8-dependent ALK5-SMAD2/3 induction of MMP2 supports the trophoblast invasion/migration phenotype in HTR-8/SVneo cells. This is a defined downstream cellular context. Supporting Evidence: PMID:34432647 the stimulatory effect of GDF-8 on MMP2 expression is mediated by the ALK5-SMAD2/3 signaling pathway. |
| GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding | IEA GO_REF:0000107 | ACCEPT | Summary: Cooperation with sequence-specific RNA polymerase II transcription factors is essential to selecting target genes; FOXH1 and MEF2 provide experimentally supported examples. Reason: Cooperation with sequence-specific RNA polymerase II transcription factors is essential to selecting target genes; FOXH1 and MEF2 provide experimentally supported examples. Supporting Evidence: PMID:9702198 hFAST-1 shared with xFAST-1 the ability to bind to human Smad2 and activate an activin response element (ARE). PMID:11160896 We have also observed in vivo interactions between Smad2 and MEF2A using co-immunoprecipitation assays. |
| GO:0062009 secondary palate development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The Smad2/4-LEF1 pathway is experimentally implicated in mouse palatal fusion and epithelial remodeling. Reason: The Smad2/4-LEF1 pathway is experimentally implicated in mouse palatal fusion and epithelial remodeling. Transfer to human is plausible conserved developmental biology, kept as tissue-specific rather than the molecular core. Supporting Evidence: PMID:14691138 Our paper is the first to show that the Smad2,4/LEF1 complex replaces beta-catenin/LEF1 during activation of EMT in vivo by TGFbeta3. |
| GO:0062009 secondary palate development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: The Smad2/4-LEF1 pathway is experimentally implicated in mouse palatal fusion and epithelial remodeling. Reason: The Smad2/4-LEF1 pathway is experimentally implicated in mouse palatal fusion and epithelial remodeling. Transfer to human is plausible conserved developmental biology, kept as tissue-specific rather than the molecular core. Supporting Evidence: PMID:14691138 Our paper is the first to show that the Smad2,4/LEF1 complex replaces beta-catenin/LEF1 during activation of EMT in vivo by TGFbeta3. |
| GO:0070410 co-SMAD binding | IPI PMID:9111321 Heteromeric and homomeric interactions correlate with signal... | ACCEPT | Summary: Binding to the co-SMAD SMAD4 produces the central transcriptional signal-transduction complex. Reason: Binding to the co-SMAD SMAD4 produces the central transcriptional signal-transduction complex. Supporting Evidence: PMID:9311995 Smads 2 and 3 interacted with Smad4 after TbetaR activation in transfected COS cells. PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0070410 co-SMAD binding | IPI PMID:9311995 TGF-beta receptor-mediated signalling through Smad2, Smad3 a... | ACCEPT | Summary: Binding to the co-SMAD SMAD4 produces the central transcriptional signal-transduction complex. Reason: Binding to the co-SMAD SMAD4 produces the central transcriptional signal-transduction complex. Supporting Evidence: PMID:9311995 Smads 2 and 3 interacted with Smad4 after TbetaR activation in transfected COS cells. PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0070411 I-SMAD binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Interactions with inhibitory SMAD6 are a regulatory context rather than the defining transcriptional activity. Reason: Interactions with inhibitory SMAD6 are a regulatory context rather than the defining transcriptional activity. The original endothelial study used human SMAD2 and SMAD4 constructs; its Smad6/7 focus is not evidence of misattribution. Supporting Evidence: PMID:9256479 Smad6 interacted with all species tested (Smad1, Smad2, and Smad4), whereas Smad7 interacted only with Smad6 (Fig. |
| GO:0070411 I-SMAD binding | IPI PMID:9256479 Vascular MADs: two novel MAD-related genes selectively induc... | KEEP AS NON CORE | Summary: Interactions with inhibitory SMAD6 are a regulatory context rather than the defining transcriptional activity. Reason: Interactions with inhibitory SMAD6 are a regulatory context rather than the defining transcriptional activity. The original endothelial study used human SMAD2 and SMAD4 constructs; its Smad6/7 focus is not evidence of misattribution. Supporting Evidence: PMID:9256479 Smad6 interacted with all species tested (Smad1, Smad2, and Smad4), whereas Smad7 interacted only with Smad6 (Fig. |
| GO:0070412 R-SMAD binding | IPI PMID:9311995 TGF-beta receptor-mediated signalling through Smad2, Smad3 a... | ACCEPT | Summary: Activated SMAD2 associates with the R-SMAD SMAD3 as well as SMAD4; the R-SMAD interaction is directly demonstrated. Reason: Activated SMAD2 associates with the R-SMAD SMAD3 as well as SMAD4; the R-SMAD interaction is directly demonstrated. Supporting Evidence: PMID:9311995 we observed TbetaR-activation-dependent interaction between Smad2 and Smad3. |
| GO:0070723 response to cholesterol | IDA PMID:17878231 Cholesterol suppresses cellular TGF-beta responsiveness: imp... | KEEP AS NON CORE | Summary: Cholesterol treatment changes SMAD2 phosphorylation and nuclear localization by modulating receptor membrane partitioning. Reason: Cholesterol treatment changes SMAD2 phosphorylation and nuclear localization by modulating receptor membrane partitioning. This is a response context, not evidence that SMAD2 binds or metabolizes cholesterol. Supporting Evidence: PMID:17878231 cholesterol treatment suppresses or attenuates TGF-beta responsiveness in all cell types studied as determined by measuring TGF-beta-induced Smad2 phosphorylation and nuclear translocation, TGF-beta-induced PAI-1 expression, TGF-beta-induced luciferase reporter gene expression and TGF-beta-induced growth inhibition. |
| GO:0071141 SMAD protein complex | IDA PMID:18832382 HMGA2 and Smads co-regulate SNAIL1 expression during inducti... | MODIFY | Summary: The functional signaling assemblies are heteromeric SMAD protein complexes, already represented by the specific term. Reason: The functional signaling assemblies are heteromeric SMAD protein complexes, already represented by the specific term. Proposed replacements: heteromeric SMAD protein complex Supporting Evidence: PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0071142 homomeric SMAD protein complex | IPI PMID:11779503 Crystal structure of a phosphorylated Smad2. Recognition of ... | KEEP AS NON CORE | Summary: Phosphorylated SMAD2 forms a homotrimer through C-terminal phosphoserine recognition in structural assays; retain the experimentally observed complex without confusing it with the dominant SMAD2-SMAD4 heteromeric output. Reason: Phosphorylated SMAD2 forms a homotrimer through C-terminal phosphoserine recognition in structural assays; retain the experimentally observed complex without confusing it with the dominant SMAD2-SMAD4 heteromeric output. Supporting Evidence: PMID:11779503 The crystal structure of a phosphorylated Smad2, at 1.8 A resolution, reveals the formation of a homotrimer mediated by the C-terminal phosphoserine (pSer) residues. |
| GO:0071144 heteromeric SMAD protein complex | IBA GO_REF:0000033 | ACCEPT | Summary: Structural and biochemical measurements establish complexes containing phosphorylated R-SMADs and SMAD4; two R-SMAD subunits plus one SMAD4 is directly observed, without asserting that every promoter complex has identical stoichiometry. Reason: Structural and biochemical measurements establish complexes containing phosphorylated R-SMADs and SMAD4; two R-SMAD subunits plus one SMAD4 is directly observed, without asserting that every promoter complex has identical stoichiometry. Supporting Evidence: PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0071144 heteromeric SMAD protein complex | IDA PMID:21828274 HEB and E2A function as SMAD/FOXH1 cofactors. | ACCEPT | Summary: Structural and biochemical measurements establish complexes containing phosphorylated R-SMADs and SMAD4; two R-SMAD subunits plus one SMAD4 is directly observed, without asserting that every promoter complex has identical stoichiometry. Reason: Structural and biochemical measurements establish complexes containing phosphorylated R-SMADs and SMAD4; two R-SMAD subunits plus one SMAD4 is directly observed, without asserting that every promoter complex has identical stoichiometry. Supporting Evidence: PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0071144 heteromeric SMAD protein complex | IPI PMID:15350224 Structural basis of heteromeric smad protein assembly in TGF... | ACCEPT | Summary: Structural and biochemical measurements establish complexes containing phosphorylated R-SMADs and SMAD4; two R-SMAD subunits plus one SMAD4 is directly observed, without asserting that every promoter complex has identical stoichiometry. Reason: Structural and biochemical measurements establish complexes containing phosphorylated R-SMADs and SMAD4; two R-SMAD subunits plus one SMAD4 is directly observed, without asserting that every promoter complex has identical stoichiometry. Supporting Evidence: PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0071144 heteromeric SMAD protein complex | NAS PMID:16322555 Smad transcription factors. | ACCEPT | Summary: Structural and biochemical measurements establish complexes containing phosphorylated R-SMADs and SMAD4; two R-SMAD subunits plus one SMAD4 is directly observed, without asserting that every promoter complex has identical stoichiometry. Reason: Structural and biochemical measurements establish complexes containing phosphorylated R-SMADs and SMAD4; two R-SMAD subunits plus one SMAD4 is directly observed, without asserting that every promoter complex has identical stoichiometry. Supporting Evidence: PMID:15350224 Both complexes are heterotrimers, comprising two phosphorylated R-Smad subunits and one Smad4 subunit, a finding that was corroborated by isothermal titration calorimetry and mutational studies. |
| GO:0071895 odontoblast differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Mouse dental papilla experiments connect phosphorylated SMAD2 nuclear import to odontoblastic differentiation; direction varies between primary and immortalized cells, so the process is retained without universalizing a positive sign. Reason: Mouse dental papilla experiments connect phosphorylated SMAD2 nuclear import to odontoblastic differentiation; direction varies between primary and immortalized cells, so the process is retained without universalizing a positive sign. Supporting Evidence: PMID:33548622 IPO7 could bind to P-SMAD2 and affect the nuclear-cytoplasm-shuttling of P-SMAD2. |
| GO:0071895 odontoblast differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Mouse dental papilla experiments connect phosphorylated SMAD2 nuclear import to odontoblastic differentiation; direction varies between primary and immortalized cells, so the process is retained without universalizing a positive sign. Reason: Mouse dental papilla experiments connect phosphorylated SMAD2 nuclear import to odontoblastic differentiation; direction varies between primary and immortalized cells, so the process is retained without universalizing a positive sign. Supporting Evidence: PMID:33548622 IPO7 could bind to P-SMAD2 and affect the nuclear-cytoplasm-shuttling of P-SMAD2. |
| GO:0097718 disordered domain specific binding | IPI PMID:15231848 Disorder in a target for the smad2 mad homology 2 domain and... | ACCEPT | Summary: NMR and binding experiments show the SMAD2 MH2 domain recognizes the intrinsically disordered SARA SMAD-binding domain. Reason: NMR and binding experiments show the SMAD2 MH2 domain recognizes the intrinsically disordered SARA SMAD-binding domain. This is a specific docking activity in receptor access. Supporting Evidence: PMID:15231848 Our results are consistent with a series of hydrophobic patches on the MH2 that are able to recognize disordered regions of proteins. |
| GO:0140297 DNA-binding transcription factor binding | IEA GO_REF:0000120 | MODIFY | Summary: FOXH1 and MEF2 are RNA polymerase II transcription factors; refine the broad transcription-factor-binding activity to the polymerase-specific term already annotated. Reason: FOXH1 and MEF2 are RNA polymerase II transcription factors; refine the broad transcription-factor-binding activity to the polymerase-specific term already annotated. Proposed replacements: RNA polymerase II-specific DNA-binding transcription factor binding Supporting Evidence: PMID:9702198 hFAST-1 shared with xFAST-1 the ability to bind to human Smad2 and activate an activin response element (ARE). PMID:11160896 We have also observed in vivo interactions between Smad2 and MEF2A using co-immunoprecipitation assays. |
| GO:0140297 DNA-binding transcription factor binding | IPI PMID:11160896 Smad proteins function as co-modulators for MEF2 transcripti... | MODIFY | Summary: FOXH1 and MEF2 are RNA polymerase II transcription factors; refine the broad transcription-factor-binding activity to the polymerase-specific term already annotated. Reason: FOXH1 and MEF2 are RNA polymerase II transcription factors; refine the broad transcription-factor-binding activity to the polymerase-specific term already annotated. Proposed replacements: RNA polymerase II-specific DNA-binding transcription factor binding Supporting Evidence: PMID:9702198 hFAST-1 shared with xFAST-1 the ability to bind to human Smad2 and activate an activin response element (ARE). PMID:11160896 We have also observed in vivo interactions between Smad2 and MEF2A using co-immunoprecipitation assays. |
| GO:0140297 DNA-binding transcription factor binding | IPI PMID:9702198 Characterization of human FAST-1, a TGF beta and activin sig... | MODIFY | Summary: FOXH1 and MEF2 are RNA polymerase II transcription factors; refine the broad transcription-factor-binding activity to the polymerase-specific term already annotated. Reason: FOXH1 and MEF2 are RNA polymerase II transcription factors; refine the broad transcription-factor-binding activity to the polymerase-specific term already annotated. Proposed replacements: RNA polymerase II-specific DNA-binding transcription factor binding Supporting Evidence: PMID:9702198 hFAST-1 shared with xFAST-1 the ability to bind to human Smad2 and activate an activin response element (ARE). PMID:11160896 We have also observed in vivo interactions between Smad2 and MEF2A using co-immunoprecipitation assays. |
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