GO_REF:0000002
Gene Ontology annotation through association of InterPro records with GO terms
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: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:10615055
Structural basis of Smad2 recognition by the Smad anchor for receptor activation.
PMID:11160896
Smad proteins function as co-modulators for MEF2 transcriptional regulatory proteins.
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:11779503
Crystal structure of a phosphorylated Smad2. Recognition of phosphoserine by the MH2 domain and insights on Smad function in TGF-beta signaling.
PMID:12411310
Cellular response to hypoxia involves signaling via Smad proteins.
PMID:12764135
The transforming activity of Ski and SnoN is dependent on their ability to repress the activity of Smad proteins.
PMID:14555988
Differential regulation of TGF-beta signaling through Smad2, Smad3 and Smad4.
PMID:15107821
c-Ski inhibits the TGF-beta signaling pathway through stabilization of inactive Smad complexes on Smad-binding elements.
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:15231848
Disorder in a target for the smad2 mad homology 2 domain and its implications for binding and specificity.
PMID:15350224
Structural basis of heteromeric smad protein assembly in TGF-beta signaling.
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:16200078
Cloning and functional characterization of a new Ski homolog, Fussel-18, specifically expressed in neuronal tissues.
PMID:16322555
Smad transcription factors.
PMID:16751101
PPM1A functions as a Smad phosphatase to terminate TGFbeta signaling.
PMID:16806156
Epithelial and ectomesenchymal role of the type I TGF-beta receptor ALK5 during facial morphogenesis and palatal fusion.
PMID:17099224
Potentiation of Smad-mediated transcriptional activation by the RNA-binding protein RBPMS.
PMID:17239842
The left-right axis is regulated by the interplay of Coco, Xnr1 and derrière in Xenopus embryos.
PMID:17292623
Fussel-15, a novel Ski/Sno homolog protein, antagonizes BMP signaling.
PMID:17438144
Smad7 antagonizes transforming growth factor beta signaling in the nucleus by interfering with functional Smad-DNA complex formation.
PMID:17878231
Cholesterol suppresses cellular TGF-beta responsiveness: implications in atherogenesis.
PMID:18268325
IKKalpha is a critical coregulator of a Smad4-independent TGFbeta-Smad2/3 signaling pathway that controls keratinocyte differentiation.
PMID:18511908
Identification of PCTA, a TGIF antagonist that promotes PML function in TGF-beta signalling.
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:18832382
HMGA2 and Smads co-regulate SNAIL1 expression during induction of epithelial-to-mesenchymal transition.
PMID:18923419
An Id-like molecule, HHM, is a synexpression group-restricted regulator of TGF-beta signalling.
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:19345189
A Mutant-p53/Smad complex opposes p63 to empower TGFbeta-induced metastasis.
PMID:19366699
Bone morphogenetic protein (BMP) and activin type II receptors balance BMP9 signals mediated by activin receptor-like kinase-1 in human pulmonary artery endothelial cells.
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:20195357
A comprehensive resource of interacting protein regions for refining human transcription factor networks.
PMID:20211142
An atlas of combinatorial transcriptional regulation in mouse and man.
PMID:20603019
TIF1gamma controls erythroid cell fate by regulating transcription elongation.
PMID:20937913
Coupling of tandem Smad ubiquitination regulatory factor (Smurf) WW domains modulates target specificity.
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:21532621
Nodal enhances the activity of FoxO3a and its synergistic interaction with Smads to regulate cyclin G2 transcription in ovarian cancer cells.
PMID:21599657
ZNF580, a novel C2H2 zinc-finger transcription factor, interacts with the TGF-β signal molecule Smad2.
PMID:21741598
A Pin1/mutant p53 axis promotes aggressiveness in breast cancer.
PMID:21828274
HEB and E2A function as SMAD/FOXH1 cofactors.
PMID:21947082
USP15 is a deubiquitylating enzyme for receptor-activated SMADs.
PMID:21960005
PPM1A dephosphorylates RanBP3 to enable efficient nuclear export of Smad2 and Smad3.
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:22781750
Protein phosphatase 5 modulates SMAD3 function in the transforming growth factor-β pathway.
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:25241761
Using an in situ proximity ligation assay to systematically profile endogenous protein-protein interactions in a pathway network.
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:26977879
Inhibiting Drivers of Non-mutational Drug Tolerance Is a Salvage Strategy for Targeted Melanoma Therapy.
PMID:31582430
Structural basis for distinct roles of SMAD2 and SMAD3 in FOXH1 pioneer-directed TGF-β signaling.
PMID:32296183
A reference map of the human binary protein interactome.
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:40205054
Multimodal cell maps as a foundation for structural and functional genomics.
PMID:8752209
MADR2 maps to 18q21 and encodes a TGFbeta-regulated MAD-related protein that is functionally mutated in colorectal carcinoma.
PMID:8980228
MADR2 is a substrate of the TGFbeta receptor and its phosphorylation is required for nuclear accumulation and signaling.
PMID:9111321
Heteromeric and homomeric interactions correlate with signaling activity and functional cooperativity of Smad3 and Smad4/DPC4.
PMID:9256479
Vascular MADs: two novel MAD-related genes selectively inducible by flow in human vascular endothelium.
PMID:9311995
TGF-beta receptor-mediated signalling through Smad2, Smad3 and Smad4.
PMID:9389648
Dual role of the Smad4/DPC4 tumor suppressor in TGFbeta-inducible transcriptional complexes.
PMID:9436979
Smad6 inhibits BMP/Smad1 signaling by specifically competing with the Smad4 tumor suppressor.
PMID:9702198
Characterization of human FAST-1, a TGF beta and activin signal transducer.
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-1112609
POU5F1 (OCT4), SOX2, NANOG, ZSCAN10, PRDM14, SMAD2, FOXP1-ES bind the POU5F1 (OCT4) promoter
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-173542
SMURF2 ubiquitinates SMAD2
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-2176445
SMURF2 binds SMAD2
Reactome:R-HSA-2176452
Degradation of ubiquitinated SMAD2
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-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-3304394
Activated TGFBR1 cannot phosphorylate SMAD2 and SMAD3 Phosphorylation Motif Mutants
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-480204
POU5F1 (OCT4), SOX2, NANOG, KLF4, PBX1, SMAD2 bind the NANOG promoter
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-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-9731111
MAPK1 and MAPK3 phosphorylate SMAD2 and SMAD3
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-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
PMID:14656760
Smad expression during kidney development.
PMID:15084457
Combinatorial activities of Smad2 and Smad3 regulate mesoderm formation and patterning in the mouse embryo.
PMID:12842913
Cell fate decisions within the mouse organizer are governed by graded Nodal signals.
PMID:23531444
Insufficient versican cleavage and Smad2 phosphorylation results in bicuspid aortic and pulmonary valves.
file:human/SMAD2/SMAD2-notes.md
SMAD2 manual primary-source research notes
PMID:14691138
TGFbeta3 signaling activates transcription of the LEF1 gene to induce epithelial mesenchymal transformation during mouse palate development.
PMID:33548622
Effects of transforming growth factor-β1 on odontoblastic differentiation in dental papilla cells is determined by IPO7 expression level.
PMID:10647180
Crystal structure of a transcriptionally active Smad4 fragment.
PMID:9707553
Transcriptional activating activity of Smad4: roles of SMAD hetero-oligomerization and enhancement by an associating transactivator.
PMID:23649632
Smad2 is essential for maintenance of the human and mouse primed pluripotent stem cell state.
file:human/SMAD2/SMAD2-uniprot.txt
UniProt Q15796 curated record