GO_REF:0000024
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
GO_REF:0000033
Annotation inferences using phylogenetic trees
GO_REF:0000043
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
GO_REF:0000052
Gene Ontology annotation based on curation of immunofluorescence data
GO_REF:0000107
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
GO_REF:0000113
Gene Ontology annotation of human sequence-specific DNA binding transcription factors (DbTFs) based on the TFClass database
GO_REF:0000117
Electronic Gene Ontology annotations created by ARBA machine learning models
GO_REF:0000120
Combined Automated Annotation using Multiple IEA Methods
PMID:10681527
Identification and characterization of a PDZ protein that interacts with activin type II receptors.
PMID:10823886
Transforming growth factor beta -inducible independent binding of SMAD to the Smad7 promoter.
PMID:11274402
Inactivation of menin, a Smad3-interacting protein, blocks transforming growth factor type beta signaling.
PMID:11278251
Smurf1 interacts with transforming growth factor-beta type I receptor through Smad7 and induces receptor degradation.
PMID:11278756
Ski-interacting protein interacts with Smad proteins to augment transforming growth factor-beta-dependent transcription.
PMID:11387212
The adaptor molecule Disabled-2 links the transforming growth factor beta receptors to the Smad pathway.
PMID:12154125
Smad3 allostery links TGF-beta receptor kinase activation to transcriptional control.
PMID:12411310
Cellular response to hypoxia involves signaling via Smad proteins.
PMID:12446380
TGFbeta-Smad signalling in postoperative human lens epithelial cells.
PMID:12650946
Identification of three novel Smad binding proteins involved in cell polarity.
PMID:12686552
Features of a Smad3 MH1-DNA complex. Roles of water and zinc in DNA binding.
PMID:12857746
Direct interaction of Ski with either Smad3 or Smad4 is necessary and sufficient for Ski-mediated repression of transforming growth factor-beta signaling.
PMID:12874272
Requirement of the co-repressor homeodomain-interacting protein kinase 2 for ski-mediated inhibition of bone morphogenetic protein-induced transcriptional activation.
PMID:12902338
Identification of glucocorticoid receptor domains involved in transrepression of transforming growth factor-beta action.
PMID:14525983
DACH1 inhibits transforming growth factor-beta signaling through binding Smad4.
PMID:14555988
Differential regulation of TGF-beta signaling through Smad2, Smad3 and Smad4.
PMID:14612439
A novel E1A-like inhibitor of differentiation (EID) family member, EID-2, suppresses transforming growth factor (TGF)-beta signaling by blocking TGF-beta-induced formation of Smad3-Smad4 complexes.
PMID:15051726
Atrophin-1-interacting protein 4/human Itch is a ubiquitin E3 ligase for human enhancer of filamentation 1 in transforming growth factor-beta signaling pathways.
PMID:15084259
Integration of Smad and forkhead pathways in the control of neuroepithelial and glioblastoma cell proliferation.
PMID:15107418
Activin receptor-like kinase-7 induces apoptosis through activation of MAPKs in a Smad3-dependent mechanism in hepatoma cells.
PMID:15150278
Nodal and ALK7 inhibit proliferation and induce apoptosis in human trophoblast cells.
PMID:15231748
Functional proteomics mapping of a human signaling pathway.
PMID:15334054
Hepatitis C viral proteins interact with Smad3 and differentially regulate TGF-beta/Smad3-mediated transcriptional activation.
PMID:15350224
Structural basis of heteromeric smad protein assembly in TGF-beta signaling.
PMID:15527767
Proteomics-based identification of proteins interacting with Smad3: SREBP-2 forms a complex with Smad3 and inhibits its transcriptional activity.
PMID:15588252
The Smad3 linker region contains a transcriptional activation domain.
PMID:15647271
The integral inner nuclear membrane protein MAN1 physically interacts with the R-Smad proteins to repress signaling by the transforming growth factor-{beta} superfamily of cytokines.
PMID:15781469
CHIP controls the sensitivity of transforming growth factor-beta signaling by modulating the basal level of Smad3 through ubiquitin-mediated degradation.
PMID:15799969
Nuclear targeting of transforming growth factor-beta-activated Smad complexes.
PMID:15897867
Oligomerization of Evi-1 regulated by the PR domain contributes to recruitment of corepressor CtBP.
PMID:16007207
Hepatitis C virus core variants isolated from liver tumor but not from adjacent non-tumor tissue interact with Smad3 and inhibit the TGF-beta pathway.
PMID:16200078
Cloning and functional characterization of a new Ski homolog, Fussel-18, specifically expressed in neuronal tissues.
PMID:16751101
PPM1A functions as a Smad phosphatase to terminate TGFbeta signaling.
PMID:16777850
The novel PIAS-like protein hZimp10 enhances Smad transcriptional activity.
PMID:16886151
Association of polymorphisms of IGF1R and genes in the transforming growth factor- beta /bone morphogenetic protein pathway with bacteremia in sickle cell anemia.
PMID:17099224
Potentiation of Smad-mediated transcriptional activation by the RNA-binding protein RBPMS.
PMID:17251190
The MH1 domain of Smad3 interacts with Pax6 and represses autoregulation of the Pax6 P1 promoter.
PMID:17292623
Fussel-15, a novel Ski/Sno homolog protein, antagonizes BMP signaling.
PMID:17469184
Involvement of the constitutive complex formation of c-Ski/SnoN with Smads in the impaired negative feedback regulation of transforming growth factor beta signaling in scleroderma fibroblasts.
PMID:17785517
Msk is required for nuclear import of TGF-{beta}/BMP-activated Smads.
PMID:18505915
Transforming growth factor-beta1, transforming growth factor-beta2, and transforming growth factor-beta3 enhance ovarian cancer metastatic potential by inducing a Smad3-dependent epithelial-to-mesenchymal transition.
PMID:18548003
SMAD proteins control DROSHA-mediated microRNA maturation.
PMID:18568018
TAZ controls Smad nucleocytoplasmic shuttling and regulates human embryonic stem-cell self-renewal.
PMID:18729074
Identification of novel Smad2 and Smad3 associated proteins in response to TGF-beta1.
PMID:18794808
Ligand-dependent ubiquitination of Smad3 is regulated by casein kinase 1 gamma 2, an inhibitor of TGF-beta signaling.
PMID:18832382
HMGA2 and Smads co-regulate SNAIL1 expression during induction of epithelial-to-mesenchymal transition.
PMID:19018011
Holding their own: the noncanonical roles of Smad proteins.
PMID:19032343
Ski co-repressor complexes maintain the basal repressed state of the TGF-beta target gene, SMAD7, via HDAC3 and PRMT5.
PMID:19049980
SKI and MEL1 cooperate to inhibit transforming growth factor-beta signal in gastric cancer cells.
PMID:19122240
Pin1 down-regulates transforming growth factor-beta (TGF-beta) signaling by inducing degradation of Smad proteins.
PMID:19135894
FAM/USP9x, a deubiquitinating enzyme essential for TGFbeta signaling, controls Smad4 monoubiquitination.
PMID:19289081
Nuclear export of Smad2 and Smad3 by RanBP3 facilitates termination of TGF-beta signaling.
PMID:19816956
MiR-21 regulates adipogenic differentiation through the modulation of TGF-beta signaling in mesenchymal stem cells derived from human adipose tissue.
PMID:20061380
MTMR4 attenuates transforming growth factor beta (TGFbeta) signaling by dephosphorylating R-Smads in endosomes.
PMID:20129061
TMEPAI, a transmembrane TGF-beta-inducible protein, sequesters Smad proteins from active participation in TGF-beta signaling.
PMID:20211142
An atlas of combinatorial transcriptional regulation in mouse and man.
PMID:20935647
IL-37 is a fundamental inhibitor of innate immunity.
PMID:21145499
The Crumbs complex couples cell density sensing to Hippo-dependent control of the TGF-β-SMAD pathway.
PMID:21258410
Selective targeting of activating and inhibitory Smads by distinct WWP2 ubiquitin ligase isoforms differentially modulates TGFβ signalling and EMT.
PMID:21297662
Homeodomain protein DLX4 counteracts key transcriptional control mechanisms of the TGF-β cytostatic program and blocks the antiproliferative effect of TGF-β.
PMID:21307346
Response gene to complement 32 interacts with Smad3 to promote epithelial-mesenchymal transition of human renal tubular cells.
PMID:21532621
Nodal enhances the activity of FoxO3a and its synergistic interaction with Smads to regulate cyclin G2 transcription in ovarian cancer cells.
PMID:21597466
Antagonistic regulation of EMT by TIF1γ and Smad4 in mammary epithelial cells.
PMID:21828274
HEB and E2A function as SMAD/FOXH1 cofactors.
PMID:21947082
USP15 is a deubiquitylating enzyme for receptor-activated SMADs.
PMID:21988832
Toward an understanding of the protein interaction network of the human liver.
PMID:22045334
Ablation of Smurf2 reveals an inhibition in TGF-β signalling through multiple mono-ubiquitination of Smad3.
PMID:22155034
Bone morphogenetic protein-3b (BMP-3b) inhibits osteoblast differentiation via Smad2/3 pathway by counteracting Smad1/5/8 signaling.
PMID:22442258
Intercellular variation in signaling through the TGF-β pathway and its relation to cell density and cell cycle phase.
PMID:22538441
CSMD1 exhibits antitumor activity in A375 melanoma cells through activation of the Smad pathway.
PMID:23723426
Kindlin-2 mediates activation of TGF-β/Smad signaling and renal fibrosis.
PMID:24378993
Crosstalk between TGF-β/Smad3 and BMP/BMPR2 signaling pathways via miR-17-92 cluster in carotid artery restenosis.
PMID:24613385
Hsp70 and Hsp90 oppositely regulate TGF-β signaling through CHIP/Stub1.
PMID:24627487
C18 ORF1, a novel negative regulator of transforming growth factor-β signaling.
PMID:24964035
Pin1 promotes degradation of Smad proteins and their interaction with phosphorylated tau in Alzheimer's disease.
PMID:25060702
A Smad3 and TTF-1/NKX2-1 complex regulates Smad4-independent gene expression.
PMID:25416956
A proteome-scale map of the human interactome network.
PMID:25502805
A massively parallel pipeline to clone DNA variants and examine molecular phenotypes of human disease mutations.
PMID:25556234
New host factors important for respiratory syncytial virus (RSV) replication revealed by a novel microfluidics screen for interactors of matrix (M) protein.
PMID:25605017
Reduction of miR-29c enhances pancreatic cancer cell migration and stem cell-like phenotype.
PMID:25609649
Proteomic analyses reveal distinct chromatin-associated and soluble transcription factor complexes.
PMID:25670079
14-3-3ζ turns TGF-β's function from tumor suppressor to metastasis promoter in breast cancer by contextual changes of Smad partners from p53 to Gli2.
PMID:25893292
Syntenin regulates TGF-β1-induced Smad activation and the epithelial-to-mesenchymal transition by inhibiting caveolin-mediated TGF-β type I receptor internalization.
PMID:25910212
Widespread macromolecular interaction perturbations in human genetic disorders.
PMID:26311719
MicroRNA-143 Activation Regulates Smooth Muscle and Endothelial Cell Crosstalk in Pulmonary Arterial Hypertension.
PMID:26680585
ShcA Protects against Epithelial-Mesenchymal Transition through Compartmentalized Inhibition of TGF-β-Induced Smad Activation.
PMID:27038547
MiRNA-199a-5p influences pulmonary artery hypertension via downregulating Smad3.
PMID:27060871
Suppression of innate inflammation and immunity by interleukin-37.
PMID:27107012
Pooled-matrix protein interaction screens using Barcode Fusion Genetics.
PMID:28467929
PPARγ Links BMP2 and TGFβ1 Pathways in Vascular Smooth Muscle Cells, Regulating Cell Proliferation and Glucose Metabolism.
PMID:28471448
MiR-1 suppresses tumor cell proliferation in colorectal cancer by inhibition of Smad3-mediated tumor glycolysis.
PMID:29789615
IL-37 isoform D downregulates pro-inflammatory cytokines expression in a Smad3-dependent manner.
PMID:29892012
An interactome perturbation framework prioritizes damaging missense mutations for developmental disorders.
PMID:29899023
NEDD9 targets COL3A1 to promote endothelial fibrosis and pulmonary arterial hypertension.
PMID:29997244
LuTHy: a double-readout bioluminescence-based two-hybrid technology for quantitative mapping of protein-protein interactions in mammalian cells.
PMID:30729664
Novel role of the clustered miR-23b-3p and miR-27b-3p in enhanced expression of fibrosis-associated genes by targeting TGFBR3 in atrial fibroblasts.
PMID:31023188
LRP1 Deficiency in Vascular SMC Leads to Pulmonary Arterial Hypertension That Is Reversed by PPARγ Activation.
PMID:31515488
Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.
PMID:31582430
Structural basis for distinct roles of SMAD2 and SMAD3 in FOXH1 pioneer-directed TGF-β signaling.
PMID:32141990
miR-4286/TGF-β1/Smad3-Negative Feedback Loop Ameliorated Vascular Endothelial Cell Damage by Attenuating Apoptosis and Inflammatory Response.
PMID:32296183
A reference map of the human binary protein interactome.
PMID:32814053
Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
PMID:34432647
GDF-8 stimulates trophoblast cell invasion by inducing ALK5-SMAD2/3-mediated MMP2 expression.
PMID:35359452
The Interplay Between TGF-β Signaling and Cell Metabolism.
PMID:35512704
Systematic discovery of mutation-directed neo-protein-protein interactions in cancer.
PMID:39243984
Gain-of-function variants in SMAD4 compromise respiratory epithelial function.
PMID:8774881
Receptor-associated Mad homologues synergize as effectors of the TGF-beta response.
PMID:9111321
Heteromeric and homomeric interactions correlate with signaling activity and functional cooperativity of Smad3 and Smad4/DPC4.
PMID:9311995
TGF-beta receptor-mediated signalling through Smad2, Smad3 and Smad4.
PMID:9732876
Smad3 and Smad4 cooperate with c-Jun/c-Fos to mediate TGF-beta-induced transcription.
PMID:9865696
SARA, a FYVE domain protein that recruits Smad2 to the TGFbeta receptor.
PMID:9892009
Roles of pathway-specific and inhibitory Smads in activin receptor signaling.
Reactome:R-HSA-1535903
Phospho R-SMAD(SMAD2/3):CO-SMAD(SMAD4):FOXO3 binds FoxO3a-binding elements
Reactome:R-HSA-1549526
Phosphorylation of SMAD2,3 by Activin:Activin Receptor
Reactome:R-HSA-170835
An anchoring protein, ZFYVE9 (SARA), recruits SMAD2/3
Reactome:R-HSA-170847
Phosphorylated SMAD2 and SMAD3 form a complex with SMAD4
Reactome:R-HSA-170850
Phosphorylated SMAD2/3 dissociates from TGFBR
Reactome:R-HSA-170868
Activated type I receptor phosphorylates SMAD2/3 directly
Reactome:R-HSA-173481
SKI/SKIL binds SMAD complex, suppressing TGF-beta signaling
Reactome:R-HSA-173488
The SMAD2/3:SMAD4 complex transfers to the nucleus
Reactome:R-HSA-173545
Ubiquitin-dependent degradation of the SMAD complex terminates TGF-beta signaling
Reactome:R-HSA-2031355
WWTR1 binds SMAD2/3:SMAD4 heterotrimer
Reactome:R-HSA-209055
PPM1A dephosphorylates nuclear SMAD2/3
Reactome:R-HSA-2106579
WWTR1:SMAD translocates to the nucleus
Reactome:R-HSA-2127257
SMAD2/3:SMAD4 heterotrimer forms a complex with RBL1, E2F4/5 and DP1/2
Reactome:R-HSA-2176475
Phosphorylation of SMAD2 and SMAD3 linker regions by CDK8 or CDK9
Reactome:R-HSA-2176491
NEDD4L binds phosphorylated linker region of SMAD2/3
Reactome:R-HSA-2176502
NEDD4L ubiquitinates SMAD2/3
Reactome:R-HSA-2176503
Degradation of SMAD2/3:SMAD4 complex
Reactome:R-HSA-2179274
SMURF2 binds SMAD3 phosphorylated in the linker region
Reactome:R-HSA-2179276
SMURF2 monoubiquitinates SMAD3
Reactome:R-HSA-2186607
TGIF recruits HDAC1 to SMAD2/3:SMAD4 heterotrimer
Reactome:R-HSA-2186643
MEN1 binds SMAD2/3:SMAD4 heterotrimer
Reactome:R-HSA-2187309
SMAD2/3:SMAD4 heterotrimer binds SP1
Reactome:R-HSA-2187325
PARP1 ADP-ribosylates SMAD3 and SMAD4
Reactome:R-HSA-2187330
PARP1 binds SMAD2/3:SMAD4 heterotrimer
Reactome:R-HSA-2187355
PMEPA1 sequesters phosphorylated SMAD2/3
Reactome:R-HSA-2187358
PMEPA1 sequesters unphosphorylated SMAD2/3
Reactome:R-HSA-2187368
STUB1 (CHIP) ubiquitinates SMAD3
Reactome:R-HSA-2187375
SMAD3 binds STUB1 (CHIP)
Reactome:R-HSA-2187382
Degradation of ubiquitinated SMAD3
Reactome:R-HSA-2187388
PPM1A protein phosphatase binds phosphorylated SMAD2/3
Reactome:R-HSA-2187395
Dephosphorylated SMAD2/3 translocates to the cytosol
Reactome:R-HSA-2187401
MTMR4 dephosphorylates SMAD2/3
Reactome:R-HSA-2187405
MTMR4 binds phosphorylated SMAD2/3
Reactome:R-HSA-3311014
SMAD4 MH2 Domain Mutants do not bind phosphorylated SMAD2 and SMAD3
Reactome:R-HSA-3315483
Phosphorylated SMAD2/3 MH2 Domain Mutants do not bind SMAD4
Reactome:R-HSA-3656523
An anchoring protein ZFYVE9 (SARA) does not recruit SMAD2/3 to TGFB1:TGFBR2:p-TGFBR1 KD Mutants
Reactome:R-HSA-6781764
USP15 deubiquitinates SMAD1,SMAD2,SMAD3, SMAD7:SMURF,KEAP1
Reactome:R-HSA-870449
TRIM33 monoubiquitinates SMAD4
Reactome:R-HSA-870538
TRIM33 (Ectodermin) binds SMAD heterotrimer in the nucleus
Reactome:R-HSA-8878143
RUNX3 binds SMAD3 and SMAD4
Reactome:R-HSA-8878178
The complex of RUNX3, SMAD3 and SMAD4 binds the CDKN1A gene promoter
Reactome:R-HSA-8952226
RUNX3 binds the BCL2L11 (BIM) gene
Reactome:R-HSA-9008692
IL37(?-218) binds SMAD3
Reactome:R-HSA-9008928
IL37(?-218):p-S423,S425-SMAD3 translocates to the nucleus
Reactome:R-HSA-9009910
IL37(?-218) binds p-S423,S425-SMAD3
Reactome:R-HSA-9617996
FOXO1,FOXO3,FOXO4 bind p-2S-SMAD2/3:SMAD4
Reactome:R-HSA-9618004
FOXO:SMAD complex binds CDKN1A gene promoter
Reactome:R-HSA-9618021
FOXG1 binds FOXO:SMAD complexes
Reactome:R-HSA-9727922
SARS-CoV-1 SUMO1-K62-p-S177-N dimer binds to SMAD3
Reactome:R-HSA-9731111
MAPK1 and MAPK3 phosphorylate SMAD2 and SMAD3
Reactome:R-HSA-9733207
p-2S-SMAD3:p-2S-SMAD3:SMAD4 forms a complex with SP1 and EP300 at the COL1A2 gene promoter
Reactome:R-HSA-9733247
YBX1 binds COL1A2 gene promoter
Reactome:R-HSA-9736959
WWTR1:p-2S-SMAD2,3:SMAD4 binds SERPINE1 gene promoter
Reactome:R-HSA-9736970
WWTR1:p-2S-SMAD2,3:SMAD4 binds SMAD7 gene promoter
Reactome:R-HSA-9736979
p-2S-SMAD2,3:SMAD4:SP1 binds CDKN2B gene promoter
Reactome:R-HSA-9736984
p-2S-SMAD2,3:SMAD4:RBL1:E2F4,5:DP1,2 binds MYC gene promoter
Reactome:R-HSA-9736992
p-2S-SMAD2,3:SMAD4 binds JUNB gene promoter
Reactome:R-HSA-9737710
SARS-CoV-1 N binds SMAD3 and EP300 at the SERPINE1 gene promoter
Reactome:R-HSA-9823952
EOMES, SMAD2,3, and GATA6 bind the CXCR4 gene
Reactome:R-HSA-9823959
SMAD2,3 and GATA6-AS1 lncRNA bind the GATA6 gene
Reactome:R-NUL-2186736
Rnf111 binds SKI/SKIL in complex with SMAD2/3:SMAD4 upon TGF-beta stimulation
Reactome:R-NUL-2186755
Ubiquitination of SKI/SKIL by Rnf111
Reactome:R-NUL-9625758
FOXO1,FOXO3 and SMAD3 bind Trim63 gene promoter