SMAD4 is the common SMAD transcription factor shared by the TGF-beta superfamily signaling branches. It associates with activated SMAD2/3 in activin, Nodal and TGF-beta responses and with BMP-responsive SMADs in BMP signaling. These complexes accumulate in the nucleus, bind regulatory DNA and recruit transcription factors, coactivators or corepressors to control cell-specific gene programs. SMAD4 acts as a transcriptional co-SMAD rather than a receptor kinase. Its outputs include epithelial growth restraint and remodeling, developmental patterning, tissue homeostasis, and hepcidin-mediated iron regulation. Alteration of SMAD4 function disrupts these programs and contributes to juvenile polyposis and cancer; its effects on proliferation and other pathways depend on cell and signaling context.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000122 negative regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | ACCEPT | Summary: SMAD4 complexes recruit activators or repressors according to transcriptional context; negative RNA polymerase II regulation is a genuine aspect rather than inconsistent with positive target regulation. Reason: SMAD4 complexes recruit activators or repressors according to transcriptional context; negative RNA polymerase II regulation is a genuine aspect rather than inconsistent with positive target regulation. 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:0000122 negative regulation of transcription by RNA polymerase II | ISS GO_REF:0000024 | ACCEPT | Summary: SMAD4 complexes recruit activators or repressors according to transcriptional context; negative RNA polymerase II regulation is a genuine aspect rather than inconsistent with positive target regulation. Reason: SMAD4 complexes recruit activators or repressors according to transcriptional context; negative RNA polymerase II regulation is a genuine aspect rather than inconsistent with positive target regulation. 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: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:0000976 transcription cis-regulatory region binding | IDA PMID:17438144 Smad7 antagonizes transforming growth factor beta signaling ... | MODIFY | Summary: The broad regulatory-region or sequence-specific DNA-binding claim can be refined to RNA polymerase II cis-regulatory region sequence-specific DNA binding, already present and supported by direct binding assays. Reason: The broad regulatory-region or sequence-specific DNA-binding claim can be refined to RNA polymerase II cis-regulatory region sequence-specific DNA binding, already present and supported by direct binding assays. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:31582430 the full-length SMAD4 protein bound the Gsc1 probe at values between 0.15 and 0.30 Β΅M (Fig. PMID:10823886 endogenous or even transfected Smad3 cannot bind to the SBE in the absence of Smad4. |
| GO:0000977 RNA polymerase II transcription regulatory region sequence-specific DNA binding | IEA GO_REF:0000107 | MODIFY | Summary: The broad regulatory-region or sequence-specific DNA-binding claim can be refined to RNA polymerase II cis-regulatory region sequence-specific DNA binding, already present and supported by direct binding assays. Reason: The broad regulatory-region or sequence-specific DNA-binding claim can be refined to RNA polymerase II cis-regulatory region sequence-specific DNA binding, already present and supported by direct binding assays. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:31582430 the full-length SMAD4 protein bound the Gsc1 probe at values between 0.15 and 0.30 Β΅M (Fig. PMID:10823886 endogenous or even transfected Smad3 cannot bind to the SBE in the absence of Smad4. |
| 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 full-length SMAD4 protein bound the Gsc1 probe at values between 0.15 and 0.30 Β΅M (Fig. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IDA PMID:18832382 HMGA2 and Smads co-regulate SNAIL1 expression during inducti... | 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 full-length SMAD4 protein bound the Gsc1 probe at values between 0.15 and 0.30 Β΅M (Fig. |
| 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 full-length SMAD4 protein bound the Gsc1 probe at values between 0.15 and 0.30 Β΅M (Fig. |
| 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 full-length SMAD4 protein bound the Gsc1 probe at values between 0.15 and 0.30 Β΅M (Fig. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IEA GO_REF:0000107 | 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 full-length SMAD4 protein bound the Gsc1 probe at values between 0.15 and 0.30 Β΅M (Fig. |
| 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:0001222 transcription corepressor binding | IPI PMID:14612439 A novel E1A-like inhibitor of differentiation (EID) family m... | ACCEPT | Summary: Interaction with transcriptional corepressors such as EID2 contributes to context-dependent SMAD regulation. Reason: Interaction with transcriptional corepressors such as EID2 contributes to context-dependent SMAD regulation. The paper explicitly studies SMAD interactions despite strongest binding to SMAD3. Supporting Evidence: PMID:14612439 EID-2 interacts constitutively with Smad proteins, and most strongly with Smad3. |
| GO:0001223 transcription coactivator binding | IPI PMID:16777850 The novel PIAS-like protein hZimp10 enhances Smad transcript... | ACCEPT | Summary: The hZimp10/ZMIZ1 coactivator binds the SMAD4 MH2 domain and enhances SMAD transcriptional activity. Reason: The hZimp10/ZMIZ1 coactivator binds the SMAD4 MH2 domain and enhances SMAD transcriptional activity. Supporting Evidence: PMID:16777850 A protein-protein interaction between Smad3 and Smad4 with hZimp10 was identified in glutathione S-transferase-pulldown and co-immunoprecipitation assays. |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IDA PMID:18832382 HMGA2 and Smads co-regulate SNAIL1 expression during inducti... | 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. |
| 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. |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IEA GO_REF:0000107 | 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. |
| GO:0001541 ovarian follicle development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SMAD4 supports follicular development through endocrine activin-dependent FSH transcription: gonadotrope Smad4 loss impairs reproductive function. Reason: SMAD4 supports follicular development through endocrine activin-dependent FSH transcription: gonadotrope Smad4 loss impairs reproductive function. This is not inferred from ovarian expression alone, and does not establish a cell-autonomous ovarian role. Supporting Evidence: PMID:24739304 SMAD4, is absolutely required for normal FSH synthesis in both male and female mice. |
| GO:0001649 osteoblast differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SMAD4-specific knockdown suppresses ectopic ossification in a rodent model, supporting osteoblast differentiation as a physiological BMP/SMAD output. Reason: SMAD4-specific knockdown suppresses ectopic ossification in a rodent model, supporting osteoblast differentiation as a physiological BMP/SMAD output. Supporting Evidence: PMID:19940863 the Runx2- and Smad4-specific siRNAs inhibited the expression of Runx2 and Smad4 at the level of messenger RNA and protein. |
| GO:0001666 response to hypoxia | IMP PMID:12411310 Cellular response to hypoxia involves signaling via Smad pro... | UNDECIDED | Summary: The cited hypoxia paper abstract establishes SMAD2/3 and HIF1A involvement but does not reveal the SMAD4-specific experimental result. Reason: The cited hypoxia paper abstract establishes SMAD2/3 and HIF1A involvement but does not reveal the SMAD4-specific experimental result. Because the full text was not retrieved, do not dismiss the curator or infer the exact SMAD4 contribution. Supporting Evidence: PMID:12411310 Exposure of HUVECs to hypoxia resulted in phosphorylation and nuclear transportation of Smad2 and Smad3 proteins as well as stimulation of transcriptional activities of Smad3 and the transcription factor hypoxia-inducible factor-1alpha and culminated in up-regulation of TGF-beta2 gene expression. |
| GO:0001837 epithelial to mesenchymal transition | IGI PMID:23221074 MicroRNA-204-5p regulates epithelial-to-mesenchymal transiti... | KEEP AS NON CORE | Summary: SMAD4 knockdown alters TGF-beta-induced epithelial transition and migration in human epithelial cells; these are cellular-context outputs of transcriptional signaling. Reason: SMAD4 knockdown alters TGF-beta-induced epithelial transition and migration in human epithelial cells; these are cellular-context outputs of transcriptional signaling. Supporting Evidence: PMID:30741461 knocked down SMAD4 could partially reverse TGF-Ξ²-induced migration, invasion, and EMT progression in the ESCC cell line EC-1. |
| GO:0001837 epithelial to mesenchymal transition | IMP PMID:30741461 miR-130a-3p regulated TGF-Ξ²1-induced epithelial-mesenchymal ... | KEEP AS NON CORE | Summary: SMAD4 knockdown alters TGF-beta-induced epithelial transition and migration in human epithelial cells; these are cellular-context outputs of transcriptional signaling. Reason: SMAD4 knockdown alters TGF-beta-induced epithelial transition and migration in human epithelial cells; these are cellular-context outputs of transcriptional signaling. Supporting Evidence: PMID:30741461 knocked down SMAD4 could partially reverse TGF-Ξ²-induced migration, invasion, and EMT progression in the ESCC cell line EC-1. |
| GO:0003148 outflow tract septum morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The full donor paper includes conditional Smad4 inactivation in neural crest with endoglin manipulation, despite its endoglin-focused title. Reason: The full donor paper includes conditional Smad4 inactivation in neural crest with endoglin manipulation, despite its endoglin-focused title. This supports conserved outflow-tract morphogenesis, kept as a tissue-specific output. Supporting Evidence: PMID:17628518 Wnt1cre;Sm4c/n;TgEng loxP embryos demonstrated characteristic defects in the outflow tract, persistent truncus arteriosus, in which there was a loss of septation of the aorta and pulmonary trunk which form the outflow tract ( Fig. |
| GO:0003148 outflow tract septum morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: The full donor paper includes conditional Smad4 inactivation in neural crest with endoglin manipulation, despite its endoglin-focused title. Reason: The full donor paper includes conditional Smad4 inactivation in neural crest with endoglin manipulation, despite its endoglin-focused title. This supports conserved outflow-tract morphogenesis, kept as a tissue-specific output. Supporting Evidence: PMID:17628518 Wnt1cre;Sm4c/n;TgEng loxP embryos demonstrated characteristic defects in the outflow tract, persistent truncus arteriosus, in which there was a loss of septation of the aorta and pulmonary trunk which form the outflow tract ( Fig. |
| GO:0003161 cardiac conduction system development | NAS PMID:26786210 The formation and function of the cardiac conduction system. | UNDECIDED | Summary: The cited review abstract describes conduction-system regulatory networks but gives no SMAD4-specific evidence; the full relevant discussion was not retrieved. Reason: The cited review abstract describes conduction-system regulatory networks but gives no SMAD4-specific evidence; the full relevant discussion was not retrieved. This is unresolved, not a claim that the experimental literature contradicts the annotation. |
| GO:0003190 atrioventricular valve formation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The mouse conditional knockout and human GATA4 interaction study links SMAD4 to endocardial activation, proliferation, EMT and valve/septal development. Reason: The mouse conditional knockout and human GATA4 interaction study links SMAD4 to endocardial activation, proliferation, EMT and valve/septal development. Preserve the tissue-specific scope rather than treating these as universal SMAD4 outputs. Supporting Evidence: PMID:21330551 Endothelial-specific knockout of Smad4 caused an absence of valve-forming activity: Smad4-deficient endocardium was associated with acellular endocardial cushions, absent epithelial-to-mesenchymal transformation, reduced endocardial proliferation, and loss of Id2 expression in valve-forming regions. PMID:21330551 Gata4 and Smad4 cooperatively activated the Id2 promoter, that human GATA4 mutations abrogated this activity, and that Id2 deficiency in mice could cause atrioventricular septal defects. |
| GO:0003190 atrioventricular valve formation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: The mouse conditional knockout and human GATA4 interaction study links SMAD4 to endocardial activation, proliferation, EMT and valve/septal development. Reason: The mouse conditional knockout and human GATA4 interaction study links SMAD4 to endocardial activation, proliferation, EMT and valve/septal development. Preserve the tissue-specific scope rather than treating these as universal SMAD4 outputs. Supporting Evidence: PMID:21330551 Endothelial-specific knockout of Smad4 caused an absence of valve-forming activity: Smad4-deficient endocardium was associated with acellular endocardial cushions, absent epithelial-to-mesenchymal transformation, reduced endocardial proliferation, and loss of Id2 expression in valve-forming regions. PMID:21330551 Gata4 and Smad4 cooperatively activated the Id2 promoter, that human GATA4 mutations abrogated this activity, and that Id2 deficiency in mice could cause atrioventricular septal defects. |
| GO:0003198 epithelial to mesenchymal transition involved in endocardial cushion formation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The mouse conditional knockout and human GATA4 interaction study links SMAD4 to endocardial activation, proliferation, EMT and valve/septal development. Reason: The mouse conditional knockout and human GATA4 interaction study links SMAD4 to endocardial activation, proliferation, EMT and valve/septal development. Preserve the tissue-specific scope rather than treating these as universal SMAD4 outputs. Supporting Evidence: PMID:21330551 Endothelial-specific knockout of Smad4 caused an absence of valve-forming activity: Smad4-deficient endocardium was associated with acellular endocardial cushions, absent epithelial-to-mesenchymal transformation, reduced endocardial proliferation, and loss of Id2 expression in valve-forming regions. PMID:21330551 Gata4 and Smad4 cooperatively activated the Id2 promoter, that human GATA4 mutations abrogated this activity, and that Id2 deficiency in mice could cause atrioventricular septal defects. |
| GO:0003220 left ventricular cardiac muscle tissue morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Myocardial SMAD4 supports ventricular septation and ventricular wall morphogenesis in mouse embryos. Reason: Early myocardial Smad4 deletion in mouse embryos produces ventricular septal defects, reduced trabeculation and thinning of the compact ventricular myocardium. This independently supports the transferred ventricular morphogenesis role. The late cardiomyocyte deletion study primarily establishes adult remodeling, so the developmental claim is grounded in the early-deletion experiment. Supporting Evidence: PMID:20877696 myocardial Smad4 conditional knockout fetuses exhibited cardiac defects, including double-outlet right ventricle (DORV) (Fig. 4D,H), ventricular septal defect (VSD) (Fig. 4D,H), decreased density of trabeculae in the ventricles and thinning of the compact layer of the ventricular myocardium (Fig. 4B,D,H,F). |
| GO:0003220 left ventricular cardiac muscle tissue morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Myocardial SMAD4 supports ventricular septation and ventricular wall morphogenesis in mouse embryos. Reason: Early myocardial Smad4 deletion in mouse embryos produces ventricular septal defects, reduced trabeculation and thinning of the compact ventricular myocardium. This independently supports the transferred ventricular morphogenesis role. The late cardiomyocyte deletion study primarily establishes adult remodeling, so the developmental claim is grounded in the early-deletion experiment. Supporting Evidence: PMID:20877696 myocardial Smad4 conditional knockout fetuses exhibited cardiac defects, including double-outlet right ventricle (DORV) (Fig. 4D,H), ventricular septal defect (VSD) (Fig. 4D,H), decreased density of trabeculae in the ventricles and thinning of the compact layer of the ventricular myocardium (Fig. 4B,D,H,F). |
| GO:0003279 cardiac septum development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The mouse conditional knockout and human GATA4 interaction study links SMAD4 to endocardial activation, proliferation, EMT and valve/septal development. Reason: The mouse conditional knockout and human GATA4 interaction study links SMAD4 to endocardial activation, proliferation, EMT and valve/septal development. Preserve the tissue-specific scope rather than treating these as universal SMAD4 outputs. Supporting Evidence: PMID:21330551 Endothelial-specific knockout of Smad4 caused an absence of valve-forming activity: Smad4-deficient endocardium was associated with acellular endocardial cushions, absent epithelial-to-mesenchymal transformation, reduced endocardial proliferation, and loss of Id2 expression in valve-forming regions. PMID:21330551 Gata4 and Smad4 cooperatively activated the Id2 promoter, that human GATA4 mutations abrogated this activity, and that Id2 deficiency in mice could cause atrioventricular septal defects. |
| 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 full-length SMAD4 protein bound the Gsc1 probe at values between 0.15 and 0.30 Β΅M (Fig. |
| GO:0003677 DNA binding | IEA GO_REF:0000120 | 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 full-length SMAD4 protein bound the Gsc1 probe at values between 0.15 and 0.30 Β΅M (Fig. |
| 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:0003700 DNA-binding transcription factor activity | IDA PMID:10823886 Transforming growth factor beta -inducible independent bindi... | 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: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 | IEA GO_REF:0000107 | 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:0005515 protein binding | IPI PMID:11278302 Transforming growth factor-beta receptor-associated protein ... | 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:11278302. Assayed/reported partner: UniProtKB:Q8WUH2. |
| 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:Q15796. |
| GO:0005515 protein binding | IPI PMID:11779505 Structural basis of Smad1 activation by receptor kinase phos... | 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:11779505. Assayed/reported partner: UniProtKB:Q15797. |
| GO:0005515 protein binding | IPI PMID:12419246 Structural mechanism of Smad4 recognition by the nuclear onc... | 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:12419246. Assayed/reported partner: UniProtKB:P12755. |
| GO:0005515 protein binding | IPI PMID:14525983 DACH1 inhibits transforming growth factor-beta signaling thr... | 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:14525983. Assayed/reported partner: UniProtKB:P12755. |
| GO:0005515 protein binding | IPI PMID:14525983 DACH1 inhibits transforming growth factor-beta signaling thr... | 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:14525983. Assayed/reported partner: UniProtKB:Q9UI36. |
| GO:0005515 protein binding | IPI PMID:14671321 Homeoprotein DLX-1 interacts with Smad4 and blocks a signali... | 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:14671321. Assayed/reported partner: UniProtKB:P56177. |
| GO:0005515 protein binding | IPI PMID:15084259 Integration of Smad and forkhead pathways in the control 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:15084259. Assayed/reported partner: UniProtKB:O43524. |
| GO:0005515 protein binding | IPI PMID:15084259 Integration of Smad and forkhead pathways in the control 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:15084259. Assayed/reported partner: UniProtKB:P98177. |
| GO:0005515 protein binding | IPI PMID:15084259 Integration of Smad and forkhead pathways in the control 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:15084259. Assayed/reported partner: UniProtKB:Q12778. |
| 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: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: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:P63279. |
| 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:P84022. |
| 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:Q15796. |
| 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:Q15797. |
| 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:Q969H4. |
| 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:Q9NPI6. |
| 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:P84022. |
| 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:Q15796. |
| GO:0005515 protein binding | IPI PMID:15881652 Tsc-22 enhances TGF-beta signaling by associating with Smad4... | 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:15881652. Assayed/reported partner: UniProtKB:Q15714. |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein 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:16189514. Assayed/reported partner: UniProtKB:O15198. |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein 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:16189514. Assayed/reported partner: UniProtKB:P63279. |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein 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:16189514. Assayed/reported partner: UniProtKB:Q01844. |
| GO:0005515 protein binding | IPI PMID:16865698 Acute myelogenous leukemia-derived SMAD4 mutations target 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:16865698. Assayed/reported partner: UniProtKB:Q13309. |
| GO:0005515 protein binding | IPI PMID:16865698 Acute myelogenous leukemia-derived SMAD4 mutations target 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:16865698. Assayed/reported partner: UniProtKB:Q9Y297. |
| 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:17183365 Control of prostate cell growth: BMP antagonizes androgen mi... | 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:17183365. Assayed/reported partner: UniProtKB:Q15797. |
| GO:0005515 protein binding | IPI PMID:17469184 Involvement of the constitutive complex formation of c-Ski/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:17469184. Assayed/reported partner: UniProtKB:P12755. |
| GO:0005515 protein binding | IPI PMID:17469184 Involvement of the constitutive complex formation of c-Ski/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:17469184. Assayed/reported partner: UniProtKB:P12757-1. |
| 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:Q15796. |
| 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: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:Q15796. |
| 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: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: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:P70398. |
| 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:P84022. |
| 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:Q15796. |
| 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:Q93008. |
| 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: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:P23769. |
| 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:P84022. |
| 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:Q15796. |
| 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: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:P08047. |
| 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:P84022. |
| 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:Q15796. |
| 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:Q92988. |
| 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:O43524. |
| 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:P84022. |
| 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:Q15796. |
| GO:0005515 protein binding | IPI PMID:21597466 Antagonistic regulation of EMT by TIF1Ξ³ and Smad4 in mammary... | 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:21597466. Assayed/reported partner: UniProtKB:P84022. |
| GO:0005515 protein binding | IPI PMID:21597466 Antagonistic regulation of EMT by TIF1Ξ³ and Smad4 in mammary... | 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:21597466. Assayed/reported partner: UniProtKB:Q9UPN9. |
| 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:P23769. |
| 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:P63279. |
| 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:Q04206. |
| 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:Q15796. |
| 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:Q9UBE8. |
| 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:P84022. |
| 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:P84022. |
| 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:Q15796. |
| GO:0005515 protein binding | IPI PMID:23201680 COUP-TFII inhibits TGF-Ξ²-induced growth barrier to promote p... | 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:23201680. Assayed/reported partner: UniProtKB:P24468. |
| GO:0005515 protein binding | IPI PMID:23397142 Analysis of protein-protein interactions in cross-talk 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:23397142. Assayed/reported partner: UniProtKB:P31749. |
| GO:0005515 protein binding | IPI PMID:23602568 The protein interaction landscape of the human CMGC kinase g... | 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:23602568. Assayed/reported partner: UniProtKB:Q9UBE8. |
| GO:0005515 protein binding | IPI PMID:24412244 Charting the molecular links between driver and susceptibili... | 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:24412244. Assayed/reported partner: UniProtKB:P01112. |
| GO:0005515 protein binding | IPI PMID:24412244 Charting the molecular links between driver and susceptibili... | 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:24412244. Assayed/reported partner: UniProtKB:P29353. |
| GO:0005515 protein binding | IPI PMID:24412244 Charting the molecular links between driver and susceptibili... | 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:24412244. Assayed/reported partner: UniProtKB:Q00597. |
| GO:0005515 protein binding | IPI PMID:24412244 Charting the molecular links between driver and susceptibili... | 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:24412244. Assayed/reported partner: UniProtKB:Q15797. |
| GO:0005515 protein binding | IPI PMID:25310401 Sustained induction of collagen synthesis by TGF-Ξ² requires ... | 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:25310401. Assayed/reported partner: UniProtKB:Q96BA8. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | 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:25416956. Assayed/reported partner: UniProtKB:P61968. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | 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:25416956. Assayed/reported partner: UniProtKB:Q8WWW0. |
| GO:0005515 protein binding | IPI PMID:25502805 A massively parallel pipeline to clone DNA variants and exam... | 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:25502805. Assayed/reported partner: UniProtKB:O15198. |
| GO:0005515 protein binding | IPI PMID:25502805 A massively parallel pipeline to clone DNA variants and exam... | 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:25502805. Assayed/reported partner: UniProtKB:P61968. |
| GO:0005515 protein binding | IPI PMID:25502805 A massively parallel pipeline to clone DNA variants and exam... | 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:25502805. Assayed/reported partner: UniProtKB:P84022. |
| GO:0005515 protein binding | IPI PMID:25502805 A massively parallel pipeline to clone DNA variants and exam... | 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:25502805. Assayed/reported partner: UniProtKB:Q8WWW0. |
| GO:0005515 protein binding | IPI PMID:25514493 Pokemon (FBI-1) interacts with Smad4 to repress TGF-Ξ²-induce... | 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:25514493. Assayed/reported partner: UniProtKB:O95365. |
| 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:O15198. |
| 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:P12755. |
| 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:P12757. |
| 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:P84022. |
| 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:Q15796. |
| 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:Q9NPI6. |
| GO:0005515 protein binding | IPI PMID:25910212 Widespread macromolecular interaction perturbations in human... | 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:25910212. Assayed/reported partner: UniProtKB:P84022. |
| GO:0005515 protein binding | IPI PMID:26878725 Mutations in nuclear pore genes NUP93, NUP205 and XPO5 cause... | 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:26878725. Assayed/reported partner: UniProtKB:O95373. |
| GO:0005515 protein binding | IPI PMID:26878725 Mutations in nuclear pore genes NUP93, NUP205 and XPO5 cause... | 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:26878725. Assayed/reported partner: UniProtKB:Q8N1F7. |
| GO:0005515 protein binding | IPI PMID:26878725 Mutations in nuclear pore genes NUP93, NUP205 and XPO5 cause... | 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:26878725. Assayed/reported partner: UniProtKB:Q9HAV4. |
| 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:27107012 Pooled-matrix protein interaction screens using Barcode Fusi... | 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:27107012. Assayed/reported partner: UniProtKB:P84022. |
| GO:0005515 protein binding | IPI PMID:27107012 Pooled-matrix protein interaction screens using Barcode Fusi... | 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:27107012. Assayed/reported partner: UniProtKB:Q9NPI6. |
| GO:0005515 protein binding | IPI PMID:29892012 An interactome perturbation framework prioritizes damaging m... | 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:29892012. Assayed/reported partner: UniProtKB:P63279. |
| GO:0005515 protein binding | IPI PMID:29892012 An interactome perturbation framework prioritizes damaging m... | 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:29892012. Assayed/reported partner: UniProtKB:P84022. |
| GO:0005515 protein binding | IPI PMID:29892012 An interactome perturbation framework prioritizes damaging m... | 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:29892012. Assayed/reported partner: UniProtKB:Q01844. |
| GO:0005515 protein binding | IPI PMID:29997244 LuTHy: a double-readout bioluminescence-based two-hybrid tec... | 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:29997244. Assayed/reported partner: UniProtKB:P84022. |
| GO:0005515 protein binding | IPI PMID:31467278 Maximizing binary interactome mapping with a minimal number ... | 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:31467278. Assayed/reported partner: UniProtKB:Q15797. |
| GO:0005515 protein binding | IPI PMID:31467278 Maximizing binary interactome mapping with a minimal number ... | 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:31467278. Assayed/reported partner: UniProtKB:Q9NPI6. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | 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:31515488. Assayed/reported partner: UniProtKB:O15198. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | 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:31515488. Assayed/reported partner: UniProtKB:P61968. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | 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:31515488. Assayed/reported partner: UniProtKB:P63279. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | 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:31515488. Assayed/reported partner: UniProtKB:P84022. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | 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:31515488. Assayed/reported partner: UniProtKB:Q01844. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | 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:31515488. Assayed/reported partner: UniProtKB:Q8WWW0. |
| 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:O15198-2. |
| 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:P43268-3. |
| 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:P61968. |
| 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:P84022. |
| 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:Q08117-2. |
| 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:Q15797. |
| 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:Q15915. |
| 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:Q8NI38. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | 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:32814053. Assayed/reported partner: UniProtKB:P05067. |
| 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:Q15796. |
| 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:O00743. |
| 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:O15524. |
| 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:O43524. |
| 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:O95754. |
| 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:O95835. |
| 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:P01112. |
| 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:P04049. |
| 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:P10398. |
| 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:P16473. |
| 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:P20823. |
| 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:P21860. |
| 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:P21912. |
| 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:P23458. |
| 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:P23769. |
| 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:P24385. |
| 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:P28340. |
| 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:P29320. |
| 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:P29353. |
| 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:P29474. |
| 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:P31749. |
| 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:P36896. |
| 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:P42338. |
| 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:P49841. |
| 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:P52333. |
| 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:P62324. |
| 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:P78333. |
| 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:P84022. |
| 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:Q00534. |
| 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:Q00597. |
| 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:Q04206. |
| 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:Q04721. |
| 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:Q12778. |
| 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:Q13309. |
| 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:Q13547. |
| 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:Q14344. |
| 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:Q15796. |
| 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:Q15797. |
| 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:Q16620. |
| 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:Q16633. |
| 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:Q8N653. |
| 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:Q8NHQ8. |
| 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:Q8TE49. |
| 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:Q8WWW0. |
| 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:Q8WZ60. |
| 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:Q92747. |
| 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:Q969H4. |
| 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:Q96HB5. |
| 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:Q9GZV9. |
| 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:Q9NW38. |
| 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:Q9NXR7. |
| 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:Q9P2J3. |
| 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:Q9UI36. |
| 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:Q9UPY6. |
| 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:Q9Y2T1. |
| 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:Q9Y6X2. |
| GO:0005515 protein binding | IPI PMID:39243984 Gain-of-function variants in SMAD4 compromise respiratory ep... | 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:39243984. Assayed/reported partner: UniProtKB:P84022. |
| 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:P12755. |
| 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:P12757. |
| 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:Q15796. |
| 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:Q15796. |
| GO:0005515 protein binding | IPI PMID:9436979 Smad6 inhibits BMP/Smad1 signaling by specifically competing... | 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:9436979. Assayed/reported partner: UniProtKB:Q15797. |
| GO:0005515 protein binding | IPI PMID:9707553 Transcriptional activating activity of Smad4: roles of SMAD ... | 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:9707553. Assayed/reported partner: UniProtKB:Q99966. |
| GO:0005518 collagen binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The donor study directly assayed collagen binding to SMAD4 MH2 and full-length protein in vitro. Reason: The donor study directly assayed collagen binding to SMAD4 MH2 and full-length protein in vitro. Retain the specific experimental binding activity, while noting that physiological contact between intracellular SMAD4 and extracellular collagen is unresolved. Supporting Evidence: PMID:14559231 Each collagen also bound to the MH2 domains of Smads 4 and 7 and, to a lesser extent, full-length Smads 1, 2, 3, and 4. |
| GO:0005634 nucleus | EXP PMID:15799969 Nuclear targeting of transforming growth factor-beta-activat... | 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:12161428 Transforming growth factor-beta inhibits pulmonary surfactan... | 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:16007207 Hepatitis C virus core variants isolated from liver tumor bu... | 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-201423 | 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-201425 | 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-201472 | 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-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-870477 | 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-8877941 | 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-8878013 | 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-8878143 | 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-8878178 | 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-8952226 | 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-9733207 | 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-9733247 | 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-9737710 | 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:0005667 transcription regulator complex | IPI PMID:12374795 Stoichiometry of active smad-transcription factor complexes ... | 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 | IPI PMID:12374795 Stoichiometry of active smad-transcription factor complexes ... | 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:0005737 cytoplasm | EXP PMID:15799969 Nuclear targeting of transforming growth factor-beta-activat... | 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/SMAD4/SMAD4-uniprot.txt Cytoplasmic in the absence of ligand. Migrates to the nucleus when complexed with R-SMAD |
| GO:0005737 cytoplasm | EXP PMID:17327236 3-Phosphoinositide-dependent PDK1 negatively regulates trans... | 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/SMAD4/SMAD4-uniprot.txt Cytoplasmic in the absence of ligand. Migrates to the nucleus when complexed with R-SMAD |
| GO:0005737 cytoplasm | IDA PMID:12161428 Transforming growth factor-beta inhibits pulmonary surfactan... | 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/SMAD4/SMAD4-uniprot.txt Cytoplasmic in the absence of ligand. Migrates to the nucleus when complexed with R-SMAD |
| 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/SMAD4/SMAD4-uniprot.txt Cytoplasmic in the absence of ligand. Migrates to the nucleus when complexed with R-SMAD |
| 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/SMAD4/SMAD4-uniprot.txt Cytoplasmic in the absence of ligand. Migrates to the nucleus when complexed with R-SMAD |
| 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/SMAD4/SMAD4-uniprot.txt Cytoplasmic in the absence of ligand. Migrates to the nucleus when complexed with R-SMAD |
| 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/SMAD4/SMAD4-uniprot.txt Cytoplasmic in the absence of ligand. Migrates to the nucleus when complexed with R-SMAD |
| 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/SMAD4/SMAD4-uniprot.txt Cytoplasmic in the absence of ligand. Migrates to the nucleus when complexed with R-SMAD |
| 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/SMAD4/SMAD4-uniprot.txt Cytoplasmic in the absence of ligand. Migrates to the nucleus when complexed with R-SMAD |
| GO:0005829 cytosol | TAS Reactome:R-HSA-201422 | 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/SMAD4/SMAD4-uniprot.txt Cytoplasmic in the absence of ligand. Migrates to the nucleus when complexed with R-SMAD |
| GO:0005829 cytosol | TAS Reactome:R-HSA-201472 | 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/SMAD4/SMAD4-uniprot.txt Cytoplasmic in the absence of ligand. Migrates to the nucleus when complexed with R-SMAD |
| 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/SMAD4/SMAD4-uniprot.txt Cytoplasmic in the absence of ligand. Migrates to the nucleus when complexed with R-SMAD |
| 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/SMAD4/SMAD4-uniprot.txt Cytoplasmic in the absence of ligand. Migrates to the nucleus when complexed with R-SMAD |
| 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/SMAD4/SMAD4-uniprot.txt Cytoplasmic in the absence of ligand. Migrates to the nucleus when complexed with R-SMAD |
| 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/SMAD4/SMAD4-uniprot.txt Cytoplasmic in the absence of ligand. Migrates to the nucleus when complexed with R-SMAD |
| GO:0005829 cytosol | TAS Reactome:R-HSA-870437 | 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/SMAD4/SMAD4-uniprot.txt Cytoplasmic in the absence of ligand. Migrates to the nucleus when complexed with R-SMAD |
| GO:0005829 cytosol | TAS Reactome:R-HSA-870477 | 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/SMAD4/SMAD4-uniprot.txt Cytoplasmic in the absence of ligand. Migrates to the nucleus when complexed with R-SMAD |
| GO:0005829 cytosol | TAS Reactome:R-HSA-870479 | 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/SMAD4/SMAD4-uniprot.txt Cytoplasmic in the absence of ligand. Migrates to the nucleus when complexed with R-SMAD |
| GO:0006351 DNA-templated transcription | IDA PMID:11779505 Structural basis of Smad1 activation by receptor kinase phos... | 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: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:0006357 regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: Regulation of RNA polymerase II target transcription is the central molecular output of SMAD4-containing signaling complexes, with both activation and repression depending on partners. Reason: Regulation of RNA polymerase II target transcription is the central molecular output of SMAD4-containing signaling complexes, with both activation and repression depending on partners. Supporting Evidence: PMID:9707553 Hetero-oligomerization of Smad4 with the pathway-restricted SMAD proteins is essential for Smad4-mediated transcription. 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:0006879 intracellular iron ion homeostasis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Liver-specific Smad4 deletion suppresses hepcidin and causes systemic iron accumulation; SMAD4 regulates iron homeostasis transcriptionally rather than transporting or binding iron. Reason: Liver-specific Smad4 deletion suppresses hepcidin and causes systemic iron accumulation; SMAD4 regulates iron homeostasis transcriptionally rather than transporting or binding iron. Supporting Evidence: PMID:16330325 a Cre-loxP-mediated liver-specific disruption of SMAD4 results in markedly decreased hepcidin expression and accumulation of iron in many organs, which is most pronounced in liver, kidney, and pancreas. |
| GO:0006879 intracellular iron ion homeostasis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Liver-specific Smad4 deletion suppresses hepcidin and causes systemic iron accumulation; SMAD4 regulates iron homeostasis transcriptionally rather than transporting or binding iron. Reason: Liver-specific Smad4 deletion suppresses hepcidin and causes systemic iron accumulation; SMAD4 regulates iron homeostasis transcriptionally rather than transporting or binding iron. Supporting Evidence: PMID:16330325 a Cre-loxP-mediated liver-specific disruption of SMAD4 results in markedly decreased hepcidin expression and accumulation of iron in many organs, which is most pronounced in liver, kidney, and pancreas. |
| 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: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:10823886 Transforming growth factor beta -inducible independent bindi... | 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: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: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: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: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:0000107 | 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: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 | IGI PMID:22821565 Functional screening for miRNAs targeting Smad4 identified m... | 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: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:23221074 MicroRNA-204-5p regulates epithelial-to-mesenchymal transiti... | 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: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:25514493 Pokemon (FBI-1) interacts with Smad4 to repress TGF-Ξ²-induce... | 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: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:8774881 Receptor-associated Mad homologues synergize as effectors of... | 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: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 | ISS GO_REF:0000024 | 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: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: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:0008284 positive regulation of cell population proliferation | IEA GO_REF:0000107 | MODIFY | Summary: The independently traced donor evidence concerns proliferation during cardiac/endocardial morphogenesis. Reason: The independently traced donor evidence concerns proliferation during cardiac/endocardial morphogenesis. Refine the otherwise context-free positive proliferation claim to the specific developmental process already annotated. Proposed replacements: positive regulation of cell proliferation involved in heart morphogenesis Supporting Evidence: PMID:21330551 Endothelial-specific knockout of Smad4 caused an absence of valve-forming activity: Smad4-deficient endocardium was associated with acellular endocardial cushions, absent epithelial-to-mesenchymal transformation, reduced endocardial proliferation, and loss of Id2 expression in valve-forming regions. |
| GO:0008284 positive regulation of cell population proliferation | ISS GO_REF:0000024 | MODIFY | Summary: The independently traced donor evidence concerns proliferation during cardiac/endocardial morphogenesis. Reason: The independently traced donor evidence concerns proliferation during cardiac/endocardial morphogenesis. Refine the otherwise context-free positive proliferation claim to the specific developmental process already annotated. Proposed replacements: positive regulation of cell proliferation involved in heart morphogenesis Supporting Evidence: PMID:21330551 Endothelial-specific knockout of Smad4 caused an absence of valve-forming activity: Smad4-deficient endocardium was associated with acellular endocardial cushions, absent epithelial-to-mesenchymal transformation, reduced endocardial proliferation, and loss of Id2 expression in valve-forming regions. |
| GO:0009653 anatomical structure morphogenesis | IBA GO_REF:0000033 | TOO GENERAL | Summary: These true developmental umbrella terms add no specificity beyond supported cardiac, limb and renal morphogenesis annotations. Reason: These true developmental umbrella terms add no specificity beyond supported cardiac, limb and renal morphogenesis annotations. 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:21330551 Endothelial-specific knockout of Smad4 caused an absence of valve-forming activity: Smad4-deficient endocardium was associated with acellular endocardial cushions, absent epithelial-to-mesenchymal transformation, reduced endocardial proliferation, and loss of Id2 expression in valve-forming regions. PMID:23034633 Smad4 deficiency blocked the aggregation of Sox9-positive progenitors, thereby preventing chondrogenic differentiation as revealed by absence of collagen type II. PMID:15342483 removal of Smad4 in nephrogenic mesenchyme using the Bmp7(cre/+) allele leads to disorganization of the nephrogenic mesenchyme and impairment of mesenchyme induction. |
| GO:0010468 regulation of gene expression | IEA GO_REF:0000117 | MODIFY | Summary: The supported molecular output is transcriptional regulation by RNA polymerase II, already annotated; this avoids implying every possible gene-expression mechanism. Reason: The supported molecular output is transcriptional regulation by RNA polymerase II, already annotated; this avoids implying every possible gene-expression mechanism. 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:0010614 negative regulation of cardiac muscle hypertrophy | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cardiomyocyte-specific Smad4 loss produces ventricular dysfunction and hypertrophic remodeling, supporting the transferred cardiac developmental/homeostatic role. Reason: Cardiomyocyte-specific Smad4 loss produces ventricular dysfunction and hypertrophic remodeling, supporting the transferred cardiac developmental/homeostatic role. This context differs from acute BMP-driven pro-hypertrophic signaling. Supporting Evidence: PMID:16151019 the deletion of Smad4 in cardiomyocytes resulted in cardiac hypertrophy characterized by an increase in the size of cardiac myocytes, age-associated fibrosis, and reexpression of certain fetal genes. |
| GO:0010614 negative regulation of cardiac muscle hypertrophy | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Cardiomyocyte-specific Smad4 loss produces ventricular dysfunction and hypertrophic remodeling, supporting the transferred cardiac developmental/homeostatic role. Reason: Cardiomyocyte-specific Smad4 loss produces ventricular dysfunction and hypertrophic remodeling, supporting the transferred cardiac developmental/homeostatic role. This context differs from acute BMP-driven pro-hypertrophic signaling. Supporting Evidence: PMID:16151019 the deletion of Smad4 in cardiomyocytes resulted in cardiac hypertrophy characterized by an increase in the size of cardiac myocytes, age-associated fibrosis, and reexpression of certain fetal genes. |
| GO:0010628 positive regulation of gene expression | IMP PMID:26747772 MicroRNA-483-3p Inhibits Extracellular Matrix Production by ... | MODIFY | Summary: The cited trabecular-meshwork experiments address positive extracellular-matrix gene expression through SMAD4. Reason: The cited trabecular-meshwork experiments address positive extracellular-matrix gene expression through SMAD4. Refine to positive regulation of transcription by RNA polymerase II already present. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: PMID:26747772 knockdown of Smad4 reduced the levels of ECM in HTMCs. |
| GO:0010631 epithelial cell migration | IMP PMID:30741461 miR-130a-3p regulated TGF-Ξ²1-induced epithelial-mesenchymal ... | KEEP AS NON CORE | Summary: SMAD4 knockdown alters TGF-beta-induced epithelial transition and migration in human epithelial cells; these are cellular-context outputs of transcriptional signaling. Reason: SMAD4 knockdown alters TGF-beta-induced epithelial transition and migration in human epithelial cells; these are cellular-context outputs of transcriptional signaling. Supporting Evidence: PMID:30741461 knocked down SMAD4 could partially reverse TGF-Ξ²-induced migration, invasion, and EMT progression in the ESCC cell line EC-1. |
| GO:0010666 positive regulation of cardiac muscle cell apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SMAD4 antisense suppresses NO-donor-induced apoptosis of rat ventricular cardiomyocytes; the SMAD3/4 complex participates with AP1 in this contextual pro-apoptotic response. Reason: SMAD4 antisense suppresses NO-donor-induced apoptosis of rat ventricular cardiomyocytes; the SMAD3/4 complex participates with AP1 in this contextual pro-apoptotic response. Supporting Evidence: PMID:15949472 inhibition of SMAD4 synthesis using SMAD4 antisense oligonucleotides reduced the number of apoptotic cells under stimulation with SNAP from 13.3 +/- 1.2% to control levels (8 +/- 1%, p < 0.05, n = 6). |
| 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:0014898 cardiac muscle hypertrophy in response to stress | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: In neonatal rat cardiomyocytes, SMAD4 depletion reduces phenylephrine-induced hypertrophy through BMP signaling. Reason: In neonatal rat cardiomyocytes, SMAD4 depletion reduces phenylephrine-induced hypertrophy through BMP signaling. Preserve this stimulus-specific pro-hypertrophic role alongside the distinct basal anti-hypertrophic phenotype. Supporting Evidence: PMID:26873969 silencing of Smad 1 or 4 using small interfering RNA diminished the ability of phenylephrine to induce hypertrophy in NRCs. |
| GO:0030154 cell differentiation | IBA GO_REF:0000033 | TOO GENERAL | Summary: Differentiation is supported but specific endocardial and osteoblast differentiation annotations capture the meaningful contexts. Reason: Differentiation is supported but specific endocardial and osteoblast differentiation annotations capture the meaningful 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:21330551 Endothelial-specific knockout of Smad4 caused an absence of valve-forming activity: Smad4-deficient endocardium was associated with acellular endocardial cushions, absent epithelial-to-mesenchymal transformation, reduced endocardial proliferation, and loss of Id2 expression in valve-forming regions. PMID:19940863 the Runx2- and Smad4-specific siRNAs inhibited the expression of Runx2 and Smad4 at the level of messenger RNA and protein. |
| GO:0030308 negative regulation of cell growth | IDA PMID:8774881 Receptor-associated Mad homologues synergize as effectors of... | KEEP AS NON CORE | Summary: SMAD4 participates in TGF-beta-dependent growth restraint; this cytostatic outcome is context-specific and coexists with proliferative developmental programs. Reason: SMAD4 participates in TGF-beta-dependent growth restraint; this cytostatic outcome is context-specific and coexists with proliferative developmental programs. Supporting Evidence: PMID:8774881 hMAD-3 and -4 synergized to induce strong ligand-independent TGF-beta-like responses. |
| GO:0030325 adrenal gland development | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: The traced adrenal study documents developmental expression and functional activin signaling, but does not demonstrate that SMAD4 executes adrenal organ development. Reason: The traced adrenal study documents developmental expression and functional activin signaling, but does not demonstrate that SMAD4 executes adrenal organ development. Expression and steroidogenic reporter responses alone do not support this precise developmental transfer. Supporting Evidence: PMID:12844345 the elements of the activin signaling pathway are present, intact, and functional. |
| GO:0030509 BMP signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: SMAD4 is the common co-SMAD for BMP-responsive R-SMADs as well as the TGF-beta/activin branch. Reason: SMAD4 is the common co-SMAD for BMP-responsive R-SMADs as well as the TGF-beta/activin branch. Direct BMP reporter and endothelial gene-expression experiments establish this as core. Supporting Evidence: PMID:19366699 BMP9-mediated mRNA transcription, including induction of BMPR-II and endoglin, is Smad4-dependent. |
| GO:0030509 BMP signaling pathway | IDA PMID:8637600 A human Mad protein acting as a BMP-regulated transcriptiona... | ACCEPT | Summary: SMAD4 is the common co-SMAD for BMP-responsive R-SMADs as well as the TGF-beta/activin branch. Reason: SMAD4 is the common co-SMAD for BMP-responsive R-SMADs as well as the TGF-beta/activin branch. Direct BMP reporter and endothelial gene-expression experiments establish this as core. Supporting Evidence: PMID:19366699 BMP9-mediated mRNA transcription, including induction of BMPR-II and endoglin, is Smad4-dependent. |
| GO:0030509 BMP signaling pathway | IDA PMID:9389648 Dual role of the Smad4/DPC4 tumor suppressor in TGFbeta-indu... | ACCEPT | Summary: SMAD4 is the common co-SMAD for BMP-responsive R-SMADs as well as the TGF-beta/activin branch. Reason: SMAD4 is the common co-SMAD for BMP-responsive R-SMADs as well as the TGF-beta/activin branch. Direct BMP reporter and endothelial gene-expression experiments establish this as core. Supporting Evidence: PMID:19366699 BMP9-mediated mRNA transcription, including induction of BMPR-II and endoglin, is Smad4-dependent. |
| GO:0030509 BMP signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: SMAD4 is the common co-SMAD for BMP-responsive R-SMADs as well as the TGF-beta/activin branch. Reason: SMAD4 is the common co-SMAD for BMP-responsive R-SMADs as well as the TGF-beta/activin branch. Direct BMP reporter and endothelial gene-expression experiments establish this as core. Supporting Evidence: PMID:19366699 BMP9-mediated mRNA transcription, including induction of BMPR-II and endoglin, is Smad4-dependent. |
| GO:0030509 BMP signaling pathway | IGI PMID:22821565 Functional screening for miRNAs targeting Smad4 identified m... | ACCEPT | Summary: SMAD4 is the common co-SMAD for BMP-responsive R-SMADs as well as the TGF-beta/activin branch. Reason: SMAD4 is the common co-SMAD for BMP-responsive R-SMADs as well as the TGF-beta/activin branch. Direct BMP reporter and endothelial gene-expression experiments establish this as core. Supporting Evidence: PMID:19366699 BMP9-mediated mRNA transcription, including induction of BMPR-II and endoglin, is Smad4-dependent. |
| GO:0030509 BMP signaling pathway | IMP PMID:19366699 Bone morphogenetic protein (BMP) and activin type II recepto... | ACCEPT | Summary: SMAD4 is the common co-SMAD for BMP-responsive R-SMADs as well as the TGF-beta/activin branch. Reason: SMAD4 is the common co-SMAD for BMP-responsive R-SMADs as well as the TGF-beta/activin branch. Direct BMP reporter and endothelial gene-expression experiments establish this as core. Supporting Evidence: PMID:19366699 BMP9-mediated mRNA transcription, including induction of BMPR-II and endoglin, is Smad4-dependent. |
| GO:0030509 BMP signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: SMAD4 is the common co-SMAD for BMP-responsive R-SMADs as well as the TGF-beta/activin branch. Reason: SMAD4 is the common co-SMAD for BMP-responsive R-SMADs as well as the TGF-beta/activin branch. Direct BMP reporter and endothelial gene-expression experiments establish this as core. Supporting Evidence: PMID:19366699 BMP9-mediated mRNA transcription, including induction of BMPR-II and endoglin, is Smad4-dependent. |
| GO:0030511 positive regulation of transforming growth factor beta receptor signaling pathway | IDA PMID:19328798 A colorectal cancer expression profile that includes transfo... | ACCEPT | Summary: SMAD4 promotes productive TGF-beta transcriptional signaling by assembling R-SMAD complexes. Reason: SMAD4 promotes productive TGF-beta transcriptional signaling by assembling R-SMAD complexes. The BAMBI-focused source is not interpreted as disproving this well-established role when its abstract lacks SMAD4 assay detail. Supporting Evidence: PMID:9707553 Hetero-oligomerization of Smad4 with the pathway-restricted SMAD proteins is essential for Smad4-mediated transcription. 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:0031005 filamin binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: A cleaved filamin-A fragment recruits SMAD3/4 and participates in nuclear transport to the laminin-gamma1 promoter in the donor study. Reason: A cleaved filamin-A fragment recruits SMAD3/4 and participates in nuclear transport to the laminin-gamma1 promoter in the donor study. This is a specific noncanonical interaction context. Supporting Evidence: PMID:20167606 Following cleavage, there is enhanced recruitment of Smad3/4 to a C-terminal FLNa fragment with nuclear translocation and subsequent binding to the promoter region of the laminin gamma1 (lamc1) gene. |
| 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:0032909 regulation of transforming growth factor beta2 production | IMP PMID:12411310 Cellular response to hypoxia involves signaling via Smad pro... | UNDECIDED | Summary: The cited hypoxia paper abstract establishes SMAD2/3 and HIF1A involvement but does not reveal the SMAD4-specific experimental result. Reason: The cited hypoxia paper abstract establishes SMAD2/3 and HIF1A involvement but does not reveal the SMAD4-specific experimental result. Because the full text was not retrieved, do not dismiss the curator or infer the exact SMAD4 contribution. Supporting Evidence: PMID:12411310 Exposure of HUVECs to hypoxia resulted in phosphorylation and nuclear transportation of Smad2 and Smad3 proteins as well as stimulation of transcriptional activities of Smad3 and the transcription factor hypoxia-inducible factor-1alpha and culminated in up-regulation of TGF-beta2 gene expression. |
| 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 | IEA GO_REF:0000107 | 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:0035556 intracellular signal transduction | IMP PMID:22316667 Germline mutations in SMAD4 disrupt bone morphogenetic prote... | 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:0036302 atrioventricular canal development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The mouse conditional knockout and human GATA4 interaction study links SMAD4 to endocardial activation, proliferation, EMT and valve/septal development. Reason: The mouse conditional knockout and human GATA4 interaction study links SMAD4 to endocardial activation, proliferation, EMT and valve/septal development. Preserve the tissue-specific scope rather than treating these as universal SMAD4 outputs. Supporting Evidence: PMID:21330551 Endothelial-specific knockout of Smad4 caused an absence of valve-forming activity: Smad4-deficient endocardium was associated with acellular endocardial cushions, absent epithelial-to-mesenchymal transformation, reduced endocardial proliferation, and loss of Id2 expression in valve-forming regions. PMID:21330551 Gata4 and Smad4 cooperatively activated the Id2 promoter, that human GATA4 mutations abrogated this activity, and that Id2 deficiency in mice could cause atrioventricular septal defects. |
| GO:0036302 atrioventricular canal development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: The mouse conditional knockout and human GATA4 interaction study links SMAD4 to endocardial activation, proliferation, EMT and valve/septal development. Reason: The mouse conditional knockout and human GATA4 interaction study links SMAD4 to endocardial activation, proliferation, EMT and valve/septal development. Preserve the tissue-specific scope rather than treating these as universal SMAD4 outputs. Supporting Evidence: PMID:21330551 Endothelial-specific knockout of Smad4 caused an absence of valve-forming activity: Smad4-deficient endocardium was associated with acellular endocardial cushions, absent epithelial-to-mesenchymal transformation, reduced endocardial proliferation, and loss of Id2 expression in valve-forming regions. PMID:21330551 Gata4 and Smad4 cooperatively activated the Id2 promoter, that human GATA4 mutations abrogated this activity, and that Id2 deficiency in mice could cause atrioventricular septal defects. |
| GO:0042118 endothelial cell activation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The mouse conditional knockout and human GATA4 interaction study links SMAD4 to endocardial activation, proliferation, EMT and valve/septal development. Reason: The mouse conditional knockout and human GATA4 interaction study links SMAD4 to endocardial activation, proliferation, EMT and valve/septal development. Preserve the tissue-specific scope rather than treating these as universal SMAD4 outputs. Supporting Evidence: PMID:21330551 Endothelial-specific knockout of Smad4 caused an absence of valve-forming activity: Smad4-deficient endocardium was associated with acellular endocardial cushions, absent epithelial-to-mesenchymal transformation, reduced endocardial proliferation, and loss of Id2 expression in valve-forming regions. PMID:21330551 Gata4 and Smad4 cooperatively activated the Id2 promoter, that human GATA4 mutations abrogated this activity, and that Id2 deficiency in mice could cause atrioventricular septal defects. |
| GO:0042177 negative regulation of protein catabolic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SMAD3-SMAD4 complexes protect beta-catenin from ubiquitin-dependent degradation in chondrocytes. Reason: SMAD3-SMAD4 complexes protect beta-catenin from ubiquitin-dependent degradation in chondrocytes. This is stabilization of a partner, not protease-inhibitor catalytic activity. Supporting Evidence: PMID:20097766 Both Smad3 and Smad4 were required for the interaction with beta-catenin and protected beta-catenin from an ubiquitin-proteasome-dependent degradation. |
| GO:0042733 embryonic digit morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Conditional mouse Smad4 deletion blocks digit-ray condensation and chondrogenic differentiation, directly supporting the transferred limb-development role. Reason: Conditional mouse Smad4 deletion blocks digit-ray condensation and chondrogenic differentiation, directly supporting the transferred limb-development role. Supporting Evidence: PMID:23034633 Smad4 deficiency blocked the aggregation of Sox9-positive progenitors, thereby preventing chondrogenic differentiation as revealed by absence of collagen type II. |
| GO:0042802 identical protein binding | IEA GO_REF:0000107 | 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:10647180 The structure of the S4AF trimer reveals novel features important for Smad4 function. |
| GO:0042802 identical protein binding | IPI PMID:10647180 Crystal structure of a transcriptionally active Smad4 fragme... | 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:10647180 The structure of the S4AF trimer reveals novel features important for Smad4 function. |
| GO:0042802 identical protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | 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:10647180 The structure of the S4AF trimer reveals novel features important for Smad4 function. |
| GO:0042802 identical protein binding | IPI PMID:25609649 Proteomic analyses reveal distinct chromatin-associated and ... | 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:10647180 The structure of the S4AF trimer reveals novel features important for Smad4 function. |
| GO:0042802 identical protein binding | IPI PMID:35512704 Systematic discovery of mutation-directed neo-protein-protei... | 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:10647180 The structure of the S4AF trimer reveals novel features important for Smad4 function. |
| GO:0042802 identical protein binding | IPI PMID:9111321 Heteromeric and homomeric interactions correlate with signal... | 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:10647180 The structure of the S4AF trimer reveals novel features important for Smad4 function. |
| GO:0042803 protein homodimerization activity | IPI PMID:8774881 Receptor-associated Mad homologues synergize as effectors of... | UNDECIDED | Summary: SMAD4 self-association is supported, but the accessible original abstract does not resolve a homodimer stoichiometry, and the crystallographic MH2 fragment is trimeric. Reason: SMAD4 self-association is supported, but the accessible original abstract does not resolve a homodimer stoichiometry, and the crystallographic MH2 fragment is trimeric. Retain uncertainty rather than convert co-association into proof of dimerization. Supporting Evidence: PMID:10647180 The structure of the S4AF trimer reveals novel features important for Smad4 function. |
| GO:0043199 sulfate binding | IMP PMID:10647180 Crystal structure of a transcriptionally active Smad4 fragme... | MARK AS OVER ANNOTATED | Summary: Sulfate binding occurs at a crystal interface proposed to mimic recognition of phosphorylated R-SMAD tails. Reason: Sulfate binding occurs at a crystal interface proposed to mimic recognition of phosphorylated R-SMAD tails. This does not establish a physiological sulfate-binding function for SMAD4. Supporting Evidence: PMID:10647180 A tandem sulfate-ion-binding site was identified within the subunit interface, which may interact with the phosphorylated C-terminal sequence of pathway-restricted SMAD proteins. |
| GO:0043565 sequence-specific DNA binding | IDA PMID:10823886 Transforming growth factor beta -inducible independent bindi... | MODIFY | Summary: The broad regulatory-region or sequence-specific DNA-binding claim can be refined to RNA polymerase II cis-regulatory region sequence-specific DNA binding, already present and supported by direct binding assays. Reason: The broad regulatory-region or sequence-specific DNA-binding claim can be refined to RNA polymerase II cis-regulatory region sequence-specific DNA binding, already present and supported by direct binding assays. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:31582430 the full-length SMAD4 protein bound the Gsc1 probe at values between 0.15 and 0.30 Β΅M (Fig. PMID:10823886 endogenous or even transfected Smad3 cannot bind to the SBE in the absence of Smad4. |
| GO:0044877 protein-containing complex binding | IEA GO_REF:0000107 | MODIFY | Summary: The functional complex-binding evidence involves SMAD-containing transcriptional assemblies; R-SMAD binding is a more informative supported activity already present. Reason: The functional complex-binding evidence involves SMAD-containing transcriptional assemblies; R-SMAD binding is a more informative supported activity already present. Proposed replacements: R-SMAD binding Supporting Evidence: PMID:16959941 reduced binding of the transcriptional coactivator CREB-binding protein 1 to transcriptional complexes containing Smad2, Smad3, and Smad4. 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:0045892 negative regulation of DNA-templated transcription | IDA PMID:8774881 Receptor-associated Mad homologues synergize as effectors of... | MODIFY | Summary: Context-dependent repression is exerted at RNA polymerase II transcription; the specific term is already present. Reason: Context-dependent repression is exerted at RNA polymerase II transcription; the specific term is already present. Proposed replacements: negative 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:0045893 positive regulation of DNA-templated transcription | IDA PMID:8774881 Receptor-associated Mad homologues synergize as effectors of... | 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: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:9707553 Transcriptional activating activity of Smad4: roles of SMAD ... | 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:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:18832382 HMGA2 and Smads co-regulate SNAIL1 expression during inducti... | 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:0045944 positive regulation of transcription by RNA polymerase II | TAS PMID:14687659 Signal transduction of bone morphogenetic protein receptors. | 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:0000107 | MODIFY | Summary: SMAD4 binds receptor-regulated SMADs and inhibitory SMADs; replace generic family binding with the specific classes already annotated. Reason: SMAD4 binds receptor-regulated SMADs and inhibitory SMADs; replace generic family binding with the specific classes already annotated. Proposed replacements: R-SMAD binding I-SMAD binding 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:0048665 neuron fate specification | IMP PMID:22357933 miR-125 potentiates early neural specification of human embr... | KEEP AS NON CORE | Summary: miR125-dependent reduction of SMAD4 influences human embryonic stem-cell neural lineage commitment. Reason: miR125-dependent reduction of SMAD4 influences human embryonic stem-cell neural lineage commitment. The process term does not assert that SMAD4 always promotes neural differentiation; preserve this regulated cell-fate context. Supporting Evidence: PMID:22357933 This was associated with the regulation by miR-125 of SMAD4, a key regulator of pluripotent stem cell lineage commitment. |
| GO:0060391 positive regulation of SMAD protein signal transduction | IEA GO_REF:0000107 | ACCEPT | Summary: Assembly with receptor-regulated SMADs promotes their transcriptional signaling; this positive co-SMAD role is a direct function, not merely correlated phosphorylation. Reason: Assembly with receptor-regulated SMADs promotes their transcriptional signaling; this positive co-SMAD role is a direct function, not merely correlated phosphorylation. Supporting Evidence: PMID:9707553 Hetero-oligomerization of Smad4 with the pathway-restricted SMAD proteins is essential for Smad4-mediated transcription. 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:0060391 positive regulation of SMAD protein signal transduction | ISS GO_REF:0000024 | ACCEPT | Summary: Assembly with receptor-regulated SMADs promotes their transcriptional signaling; this positive co-SMAD role is a direct function, not merely correlated phosphorylation. Reason: Assembly with receptor-regulated SMADs promotes their transcriptional signaling; this positive co-SMAD role is a direct function, not merely correlated phosphorylation. Supporting Evidence: PMID:9707553 Hetero-oligomerization of Smad4 with the pathway-restricted SMAD proteins is essential for Smad4-mediated transcription. 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: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:10823886 Transforming growth factor beta -inducible independent bindi... | 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:22821565 Functional screening for miRNAs targeting Smad4 identified m... | 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:9707553 Transcriptional activating activity of Smad4: roles of SMAD ... | 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:0000107 | 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:23221074 MicroRNA-204-5p regulates epithelial-to-mesenchymal transiti... | 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:26747772 MicroRNA-483-3p Inhibits Extracellular Matrix Production by ... | 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 | ISS GO_REF:0000024 | 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:0060412 ventricular septum morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Myocardial SMAD4 supports ventricular septation and ventricular wall morphogenesis in mouse embryos. Reason: Early myocardial Smad4 deletion in mouse embryos produces ventricular septal defects, reduced trabeculation and thinning of the compact ventricular myocardium. This independently supports the transferred ventricular morphogenesis role. The late cardiomyocyte deletion study primarily establishes adult remodeling, so the developmental claim is grounded in the early-deletion experiment. Supporting Evidence: PMID:20877696 myocardial Smad4 conditional knockout fetuses exhibited cardiac defects, including double-outlet right ventricle (DORV) (Fig. 4D,H), ventricular septal defect (VSD) (Fig. 4D,H), decreased density of trabeculae in the ventricles and thinning of the compact layer of the ventricular myocardium (Fig. 4B,D,H,F). |
| GO:0060412 ventricular septum morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Myocardial SMAD4 supports ventricular septation and ventricular wall morphogenesis in mouse embryos. Reason: Early myocardial Smad4 deletion in mouse embryos produces ventricular septal defects, reduced trabeculation and thinning of the compact ventricular myocardium. This independently supports the transferred ventricular morphogenesis role. The late cardiomyocyte deletion study primarily establishes adult remodeling, so the developmental claim is grounded in the early-deletion experiment. Supporting Evidence: PMID:20877696 myocardial Smad4 conditional knockout fetuses exhibited cardiac defects, including double-outlet right ventricle (DORV) (Fig. 4D,H), ventricular septal defect (VSD) (Fig. 4D,H), decreased density of trabeculae in the ventricles and thinning of the compact layer of the ventricular myocardium (Fig. 4B,D,H,F). |
| GO:0060956 endocardial cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The mouse conditional knockout and human GATA4 interaction study links SMAD4 to endocardial activation, proliferation, EMT and valve/septal development. Reason: The mouse conditional knockout and human GATA4 interaction study links SMAD4 to endocardial activation, proliferation, EMT and valve/septal development. Preserve the tissue-specific scope rather than treating these as universal SMAD4 outputs. Supporting Evidence: PMID:21330551 Endothelial-specific knockout of Smad4 caused an absence of valve-forming activity: Smad4-deficient endocardium was associated with acellular endocardial cushions, absent epithelial-to-mesenchymal transformation, reduced endocardial proliferation, and loss of Id2 expression in valve-forming regions. PMID:21330551 Gata4 and Smad4 cooperatively activated the Id2 promoter, that human GATA4 mutations abrogated this activity, and that Id2 deficiency in mice could cause atrioventricular septal defects. |
| GO:0060956 endocardial cell differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: The mouse conditional knockout and human GATA4 interaction study links SMAD4 to endocardial activation, proliferation, EMT and valve/septal development. Reason: The mouse conditional knockout and human GATA4 interaction study links SMAD4 to endocardial activation, proliferation, EMT and valve/septal development. Preserve the tissue-specific scope rather than treating these as universal SMAD4 outputs. Supporting Evidence: PMID:21330551 Endothelial-specific knockout of Smad4 caused an absence of valve-forming activity: Smad4-deficient endocardium was associated with acellular endocardial cushions, absent epithelial-to-mesenchymal transformation, reduced endocardial proliferation, and loss of Id2 expression in valve-forming regions. PMID:21330551 Gata4 and Smad4 cooperatively activated the Id2 promoter, that human GATA4 mutations abrogated this activity, and that Id2 deficiency in mice could cause atrioventricular septal defects. |
| 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 determines target-gene selection. Reason: Cooperation with sequence-specific RNA polymerase II transcription factors determines target-gene selection. FOXH1/FAST1-dependent reporter activation requires SMAD4, and GATA4 and SMAD4 cooperate on the Id2 promoter. Supporting Evidence: PMID:9702198 The hFAST-1-dependent activation of ARE was completely dependent on endogenous Smad4 and stimulation by a TGF beta-like ligand. PMID:21330551 Gata4 and Smad4 cooperatively activated the Id2 promoter |
| 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:0070102 interleukin-6-mediated signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SMAD4 is required for the hepcidin transcriptional response to IL6 in hepatocytes. Reason: SMAD4 is required for the hepcidin transcriptional response to IL6 in hepatocytes. Retain this cross-pathway transcriptional context without presenting SMAD4 as an IL6 receptor component. Supporting Evidence: PMID:16330325 transcriptional activation of hepcidin is abrogated in SMAD4-deficient hepatocytes in response to iron overload, TGF-beta, BMP, or IL-6. |
| GO:0070102 interleukin-6-mediated signaling pathway | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SMAD4 is required for the hepcidin transcriptional response to IL6 in hepatocytes. Reason: SMAD4 is required for the hepcidin transcriptional response to IL6 in hepatocytes. Retain this cross-pathway transcriptional context without presenting SMAD4 as an IL6 receptor component. Supporting Evidence: PMID:16330325 transcriptional activation of hepcidin is abrogated in SMAD4-deficient hepatocytes in response to iron overload, TGF-beta, BMP, or IL-6. |
| GO:0070371 ERK1 and ERK2 cascade | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Dominant-negative SMAD4 blocks delayed, protein-synthesis-dependent ERK activation by TGF-beta in rat pancreatic acinar cells. Reason: Dominant-negative SMAD4 blocks delayed, protein-synthesis-dependent ERK activation by TGF-beta in rat pancreatic acinar cells. Retain the cross-pathway response, not ERK catalytic activity. Supporting Evidence: PMID:11401854 adenoviral-mediated expression of dominant negative Smad4 blocked the ability of TGF-beta to activate acinar cell MAP kinase, demonstrating that this activation is downstream of Smads. |
| GO:0070373 negative regulation of ERK1 and ERK2 cascade | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cardiomyocyte Smad4 deletion increases MEK/ERK phosphorylation, supporting restraint of the ERK cascade in that tissue. Reason: Cardiomyocyte Smad4 deletion increases MEK/ERK phosphorylation, supporting restraint of the ERK cascade in that tissue. This differs from its positive influence in pancreatic acinar cells. Supporting Evidence: PMID:16151019 phosphorylated extracellular signal-regulated kinase (ERK) 1/2 and mitogen-activated protein kinase-ERK (MEK) 1 were increased in the Smad4 mutants, suggesting that an upregulation of MEK1-ERK1/2 signaling as a consequence of deletion of Smad4 underlies the impaired cardiac function. |
| GO:0070373 negative regulation of ERK1 and ERK2 cascade | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Cardiomyocyte Smad4 deletion increases MEK/ERK phosphorylation, supporting restraint of the ERK cascade in that tissue. Reason: Cardiomyocyte Smad4 deletion increases MEK/ERK phosphorylation, supporting restraint of the ERK cascade in that tissue. This differs from its positive influence in pancreatic acinar cells. Supporting Evidence: PMID:16151019 phosphorylated extracellular signal-regulated kinase (ERK) 1/2 and mitogen-activated protein kinase-ERK (MEK) 1 were increased in the Smad4 mutants, suggesting that an upregulation of MEK1-ERK1/2 signaling as a consequence of deletion of Smad4 underlies the impaired cardiac function. |
| 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:8774881 Receptor-associated Mad homologues synergize as effectors of... | ACCEPT | Summary: Association with phosphorylated receptor-regulated SMADs is the defining co-SMAD activity; structural measurements establish the interface and heteromeric assembly. Reason: Association with phosphorylated receptor-regulated SMADs is the defining co-SMAD activity; structural measurements establish the interface and heteromeric assembly. 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:0070412 R-SMAD binding | IPI PMID:9111321 Heteromeric and homomeric interactions correlate with signal... | ACCEPT | Summary: Association with phosphorylated receptor-regulated SMADs is the defining co-SMAD activity; structural measurements establish the interface and heteromeric assembly. Reason: Association with phosphorylated receptor-regulated SMADs is the defining co-SMAD activity; structural measurements establish the interface and heteromeric assembly. 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:0070412 R-SMAD binding | IPI PMID:9111321 Heteromeric and homomeric interactions correlate with signal... | ACCEPT | Summary: Association with phosphorylated receptor-regulated SMADs is the defining co-SMAD activity; structural measurements establish the interface and heteromeric assembly. Reason: Association with phosphorylated receptor-regulated SMADs is the defining co-SMAD activity; structural measurements establish the interface and heteromeric assembly. 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:0070412 R-SMAD binding | IPI PMID:9111321 Heteromeric and homomeric interactions correlate with signal... | ACCEPT | Summary: Association with phosphorylated receptor-regulated SMADs is the defining co-SMAD activity; structural measurements establish the interface and heteromeric assembly. Reason: Association with phosphorylated receptor-regulated SMADs is the defining co-SMAD activity; structural measurements establish the interface and heteromeric assembly. 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:0070412 R-SMAD binding | IPI PMID:9311995 TGF-beta receptor-mediated signalling through Smad2, Smad3 a... | ACCEPT | Summary: Association with phosphorylated receptor-regulated SMADs is the defining co-SMAD activity; structural measurements establish the interface and heteromeric assembly. Reason: Association with phosphorylated receptor-regulated SMADs is the defining co-SMAD activity; structural measurements establish the interface and heteromeric assembly. 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:0070412 R-SMAD binding | IPI PMID:9311995 TGF-beta receptor-mediated signalling through Smad2, Smad3 a... | ACCEPT | Summary: Association with phosphorylated receptor-regulated SMADs is the defining co-SMAD activity; structural measurements establish the interface and heteromeric assembly. Reason: Association with phosphorylated receptor-regulated SMADs is the defining co-SMAD activity; structural measurements establish the interface and heteromeric assembly. 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:0070412 R-SMAD binding | IPI PMID:9732876 Smad3 and Smad4 cooperate with c-Jun/c-Fos to mediate TGF-be... | ACCEPT | Summary: Association with phosphorylated receptor-regulated SMADs is the defining co-SMAD activity; structural measurements establish the interface and heteromeric assembly. Reason: Association with phosphorylated receptor-regulated SMADs is the defining co-SMAD activity; structural measurements establish the interface and heteromeric assembly. 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: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:0071141 SMAD protein complex | IMP PMID:10647180 Crystal structure of a transcriptionally active Smad4 fragme... | 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: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 | IPI PMID:11779505 Structural basis of Smad1 activation by receptor kinase phos... | 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:0071333 cellular response to glucose stimulus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: High glucose changes SMAD4 abundance and SUMO2/3 modification in rat mesangial cells. Reason: High glucose changes SMAD4 abundance and SUMO2/3 modification in rat mesangial cells. Retain the observed cellular-response context without inferring glucose binding or sensing by SMAD4. Supporting Evidence: PMID:24941801 the sumolyation (SUMO2/3) of Smad4 was enhanced significantly in the high glucose groups compared with the control group (P < 0.05). |
| GO:0071363 cellular response to growth factor stimulus | IEA GO_REF:0000117 | MODIFY | Summary: Refine the generic growth-factor/superfamily response to the directly established TGF-beta receptor, activin receptor, and BMP signaling branches already annotated. Reason: Refine the generic growth-factor/superfamily response to the directly established TGF-beta receptor, activin receptor, and BMP signaling branches already annotated. Proposed replacements: transforming growth factor beta receptor signaling pathway activin receptor signaling pathway BMP signaling pathway Supporting Evidence: PMID:31582430 TGF-Ξ², Nodal, and Activin receptors phosphorylate SMAD2 and SMAD3. PMID:19366699 BMP9-mediated mRNA transcription, including induction of BMPR-II and endoglin, is Smad4-dependent. PMID:9702198 The hFAST-1-dependent activation of ARE was completely dependent on endogenous Smad4 and stimulation by a TGF beta-like ligand. |
| GO:0071559 response to transforming growth factor beta | IDA PMID:9707553 Transcriptional activating activity of Smad4: roles of SMAD ... | MODIFY | Summary: The demonstrated cellular response is execution of TGF-beta receptor signaling, already annotated; this is more informative than an unspecified response to stimulus. Reason: The demonstrated cellular response is execution of TGF-beta receptor signaling, already annotated; this is more informative than an unspecified response to stimulus. Proposed replacements: transforming growth factor beta receptor signaling pathway 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:0071560 cellular response to transforming growth factor beta stimulus | IMP PMID:23221074 MicroRNA-204-5p regulates epithelial-to-mesenchymal transiti... | MODIFY | Summary: The demonstrated cellular response is execution of TGF-beta receptor signaling, already annotated; this is more informative than an unspecified response to stimulus. Reason: The demonstrated cellular response is execution of TGF-beta receptor signaling, already annotated; this is more informative than an unspecified response to stimulus. Proposed replacements: transforming growth factor beta receptor signaling pathway 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:0071773 cellular response to BMP stimulus | NAS PMID:14687659 Signal transduction of bone morphogenetic protein receptors. | MODIFY | Summary: The BMP response is specifically participation in BMP signaling, already annotated. Reason: The BMP response is specifically participation in BMP signaling, already annotated. Proposed replacements: BMP signaling pathway Supporting Evidence: PMID:19366699 BMP9-mediated mRNA transcription, including induction of BMPR-II and endoglin, is Smad4-dependent. |
| GO:0072133 metanephric mesenchyme morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Mesenchyme-specific Smad4 deletion disrupts recruitment and organization around ureteric bud tips. Reason: Mesenchyme-specific Smad4 deletion disrupts recruitment and organization around ureteric bud tips. This supports the renal mesenchymal morphogenesis terms, while the same study finds collecting-duct development Smad4-independent. Supporting Evidence: PMID:15342483 removal of Smad4 in nephrogenic mesenchyme using the Bmp7(cre/+) allele leads to disorganization of the nephrogenic mesenchyme and impairment of mesenchyme induction. |
| GO:0072134 nephrogenic mesenchyme morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Mesenchyme-specific Smad4 deletion disrupts recruitment and organization around ureteric bud tips. Reason: Mesenchyme-specific Smad4 deletion disrupts recruitment and organization around ureteric bud tips. This supports the renal mesenchymal morphogenesis terms, while the same study finds collecting-duct development Smad4-independent. Supporting Evidence: PMID:15342483 removal of Smad4 in nephrogenic mesenchyme using the Bmp7(cre/+) allele leads to disorganization of the nephrogenic mesenchyme and impairment of mesenchyme induction. |
| GO:0090090 negative regulation of canonical Wnt signaling pathway | IMP PMID:23538390 microRNA-183 is an oncogene targeting Dkk-3 and SMAD4 in pro... | KEEP AS NON CORE | Summary: The full prostate-cancer study includes SMAD4 overexpression and WNT/beta-catenin assays, supporting negative regulation in that cellular context. Reason: The full prostate-cancer study includes SMAD4 overexpression and WNT/beta-catenin assays, supporting negative regulation in that cellular context. Do not generalize the sign to chondrocytes, where SMAD3/4 instead stabilize beta-catenin. Supporting Evidence: PMID:23538390 Tcf transcriptional activity was decreased to 70% in Dkk-3- or/and SMAD4-transfected PC-3 cells compared with control, indicating that Dkk-3 and SMAD4 inhibits the Ξ²-catenin-depending pathway in PC cells (Figure 7D).Effect of miR-183 on Wnt-Ξ²-catenin pathwayAs TOPflash luciferase activity was significantly decreased with Dkk-3 and SMAD4 overexpression, we also performed the same assay using miR-183 inhibitor. |
| GO:0090575 RNA polymerase II transcription regulator complex | IEA GO_REF:0000107 | ACCEPT | Summary: SMAD4 forms transcription complexes with R-SMADs and DNA-binding partners at RNA polymerase II target genes. Reason: SMAD4 forms transcription complexes with R-SMADs and DNA-binding partners at RNA polymerase II target genes. 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:21330551 Gata4 and Smad4 cooperatively activated the Id2 promoter, that human GATA4 mutations abrogated this activity, and that Id2 deficiency in mice could cause atrioventricular septal defects. |
| GO:0097191 extrinsic apoptotic signaling pathway | IMP PMID:22821565 Functional screening for miRNAs targeting Smad4 identified m... | KEEP AS NON CORE | Summary: SMAD4-mediated TGF-beta responses include ligand-induced apoptosis in gastric cancer cells, with miR199a acting upstream by repressing SMAD4. Reason: SMAD4-mediated TGF-beta responses include ligand-induced apoptosis in gastric cancer cells, with miR199a acting upstream by repressing SMAD4. Retain the contextual apoptotic signaling role without equating SMAD4 to an executioner protease. Supporting Evidence: PMID:22821565 Overexpression of miR-199a significantly inhibited the ability of TGF-Ξ² to induce gastric cancer cell growth arrest and apoptosis in vitro, and promoted anchorage-independent growth in soft agar, suggesting that miR-199a plays an oncogenic role in human gastric tumourigenesis. |
| GO:0141091 transforming growth factor beta receptor superfamily signaling pathway | IEA GO_REF:0000117 | MODIFY | Summary: Refine the generic growth-factor/superfamily response to the directly established TGF-beta receptor, activin receptor, and BMP signaling branches already annotated. Reason: Refine the generic growth-factor/superfamily response to the directly established TGF-beta receptor, activin receptor, and BMP signaling branches already annotated. Proposed replacements: transforming growth factor beta receptor signaling pathway activin receptor signaling pathway BMP signaling pathway Supporting Evidence: PMID:31582430 TGF-Ξ², Nodal, and Activin receptors phosphorylate SMAD2 and SMAD3. PMID:19366699 BMP9-mediated mRNA transcription, including induction of BMPR-II and endoglin, is Smad4-dependent. PMID:9702198 The hFAST-1-dependent activation of ARE was completely dependent on endogenous Smad4 and stimulation by a TGF beta-like ligand. |
| GO:0160108 animal gross anatomical part developmental process | IEA GO_REF:0000117 | TOO GENERAL | Summary: These true developmental umbrella terms add no specificity beyond supported cardiac, limb and renal morphogenesis annotations. Reason: These true developmental umbrella terms add no specificity beyond supported cardiac, limb and renal morphogenesis annotations. Supporting Evidence: PMID:21330551 Endothelial-specific knockout of Smad4 caused an absence of valve-forming activity: Smad4-deficient endocardium was associated with acellular endocardial cushions, absent epithelial-to-mesenchymal transformation, reduced endocardial proliferation, and loss of Id2 expression in valve-forming regions. PMID:23034633 Smad4 deficiency blocked the aggregation of Sox9-positive progenitors, thereby preventing chondrogenic differentiation as revealed by absence of collagen type II. PMID:15342483 removal of Smad4 in nephrogenic mesenchyme using the Bmp7(cre/+) allele leads to disorganization of the nephrogenic mesenchyme and impairment of mesenchyme induction. |
| GO:1901203 positive regulation of extracellular matrix assembly | IMP PMID:26747772 MicroRNA-483-3p Inhibits Extracellular Matrix Production by ... | KEEP AS NON CORE | Summary: SMAD4 knockdown reduces matrix components in human trabecular meshwork cells, supporting positive regulation of extracellular matrix production/assembly through transcription. Reason: SMAD4 knockdown reduces matrix components in human trabecular meshwork cells, supporting positive regulation of extracellular matrix production/assembly through transcription. Supporting Evidence: PMID:26747772 knockdown of Smad4 reduced the levels of ECM in HTMCs. |
| GO:1902895 positive regulation of miRNA transcription | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SMAD4-dependent transcription upregulates miR29a in human and mouse endothelial cells. Reason: SMAD4-dependent transcription upregulates miR29a in human and mouse endothelial cells. This is miRNA transcription, distinct from SMAD4-independent DROSHA processing by R-SMADs. Supporting Evidence: PMID:23426367 MiR-29a was directly up-regulated by TGF-Ξ²/Smad4 signaling in human and mice endothelial cells. |
| GO:1905305 negative regulation of cardiac myofibril assembly | IEA GO_REF:0000107 | UNDECIDED | Summary: The specific negative regulation of cardiac myofibril assembly remains unresolved. Reason: The traced mouse donor study establishes hypertrophy and contractile remodeling after cardiomyocyte Smad4 deletion. Its accessible abstract does not describe myofibril assembly measurements or establish the exact negative regulatory sign. The full original results were not retrieved, so retain uncertainty rather than infer this specific process from hypertrophy or overturn the donor curator. Supporting Evidence: PMID:16151019 the deletion of Smad4 in cardiomyocytes resulted in cardiac hypertrophy characterized by an increase in the size of cardiac myocytes, age-associated fibrosis, and reexpression of certain fetal genes. |
| GO:1905305 negative regulation of cardiac myofibril assembly | ISS GO_REF:0000024 | UNDECIDED | Summary: The specific negative regulation of cardiac myofibril assembly remains unresolved. Reason: The traced mouse donor study establishes hypertrophy and contractile remodeling after cardiomyocyte Smad4 deletion. Its accessible abstract does not describe myofibril assembly measurements or establish the exact negative regulatory sign. The full original results were not retrieved, so retain uncertainty rather than infer this specific process from hypertrophy or overturn the donor curator. Supporting Evidence: PMID:16151019 the deletion of Smad4 in cardiomyocytes resulted in cardiac hypertrophy characterized by an increase in the size of cardiac myocytes, age-associated fibrosis, and reexpression of certain fetal genes. |
| GO:2000138 positive regulation of cell proliferation involved in heart morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The mouse conditional knockout and human GATA4 interaction study links SMAD4 to endocardial activation, proliferation, EMT and valve/septal development. Reason: The mouse conditional knockout and human GATA4 interaction study links SMAD4 to endocardial activation, proliferation, EMT and valve/septal development. Preserve the tissue-specific scope rather than treating these as universal SMAD4 outputs. Supporting Evidence: PMID:21330551 Endothelial-specific knockout of Smad4 caused an absence of valve-forming activity: Smad4-deficient endocardium was associated with acellular endocardial cushions, absent epithelial-to-mesenchymal transformation, reduced endocardial proliferation, and loss of Id2 expression in valve-forming regions. PMID:21330551 Gata4 and Smad4 cooperatively activated the Id2 promoter, that human GATA4 mutations abrogated this activity, and that Id2 deficiency in mice could cause atrioventricular septal defects. |
| GO:2000138 positive regulation of cell proliferation involved in heart morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: The mouse conditional knockout and human GATA4 interaction study links SMAD4 to endocardial activation, proliferation, EMT and valve/septal development. Reason: The mouse conditional knockout and human GATA4 interaction study links SMAD4 to endocardial activation, proliferation, EMT and valve/septal development. Preserve the tissue-specific scope rather than treating these as universal SMAD4 outputs. Supporting Evidence: PMID:21330551 Endothelial-specific knockout of Smad4 caused an absence of valve-forming activity: Smad4-deficient endocardium was associated with acellular endocardial cushions, absent epithelial-to-mesenchymal transformation, reduced endocardial proliferation, and loss of Id2 expression in valve-forming regions. PMID:21330551 Gata4 and Smad4 cooperatively activated the Id2 promoter, that human GATA4 mutations abrogated this activity, and that Id2 deficiency in mice could cause atrioventricular septal defects. |
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