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Schema
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BlackBoxEvent
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Entries
The SMAD2/3:SMAD4 complex transfers to the nucleus
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authored
[InstanceEdit:171270] Heldin, CH, Moustakas, A, Huminiecki, L, Jassal, B, 2006年02月02日
category
omitted
compartment
[Compartment:70101] cytosol
[Compartment:7660] nucleoplasm
created
[InstanceEdit:173513] Jassal, B, 2006年02月10日 14:02:35
dbId
173488
displayName
The SMAD2/3:SMAD4 complex transfers to the nucleus
edited
[InstanceEdit:173513] Jassal, B, 2006年02月10日 14:02:35
[InstanceEdit:9773750] Orlic-Milacic, Marija, 2022年05月09日
eventOf
[Pathway:R-HSA-2173796] SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription - Homo sapiens
[Pathway:R-HSA-1502540] Signaling by Activin - Homo sapiens
followingEvent
[Reaction:R-HSA-1225919] Phospho R-SMAD(SMAD2,3):CO-SMAD(SMAD4):FOXH1 binds Activin Response Element - Homo sapiens
[Reaction:R-HSA-1535903] Phospho R-SMAD(SMAD2/3):CO-SMAD(SMAD4):FOXO3 binds FoxO3a-binding elements - Homo sapiens
[Reaction:R-HSA-9756948] p-2S-SMAD2,3:SMAD4, p-2S-SMAD2,3:TRIM33, CTNNB1, EOMES, and TBPL2 bind FOXH1:SMAD3:GSC gene - Homo sapiens
[Reaction:R-HSA-9823959] SMAD2,3 and GATA6-AS1 lncRNA bind the GATA6 gene - Homo sapiens
[Reaction:R-HSA-9823958] EOMES, TBXT (T BRACHYURY), GATA6, and SMAD2,3 bind the FOXA2 gene - Homo sapiens
[Reaction:R-HSA-870538] TRIM33 (Ectodermin) binds SMAD heterotrimer in the nucleus - Homo sapiens
[Reaction:R-HSA-173481] SKI/SKIL binds SMAD complex, suppressing TGF-beta signaling - Homo sapiens
[Reaction:R-HSA-2176475] Phosphorylation of SMAD2 and SMAD3 linker regions by CDK8 or CDK9 - Homo sapiens
[Reaction:R-HSA-2127257] SMAD2/3:SMAD4 heterotrimer forms a complex with RBL1, E2F4/5 and DP1/2 - Homo sapiens
[Reaction:R-HSA-9617996] FOXO1,FOXO3,FOXO4 bind p-2S-SMAD2/3:SMAD4 - Homo sapiens
[Reaction:R-HSA-2187309] SMAD2/3:SMAD4 heterotrimer binds SP1 - Homo sapiens
[Reaction:R-HSA-2186607] TGIF recruits HDAC1 to SMAD2/3:SMAD4 heterotrimer - Homo sapiens
[Reaction:R-HSA-2187330] PARP1 binds SMAD2/3:SMAD4 heterotrimer - Homo sapiens
[Reaction:R-HSA-2187388] PPM1A protein phosphatase binds phosphorylated SMAD2/3 - Homo sapiens
[BlackBoxEvent:R-HSA-173545] Ubiquitin-dependent degradation of the SMAD complex terminates TGF-beta signaling - Homo sapiens
[Reaction:R-HSA-9733207] p-2S-SMAD3:p-2S-SMAD3:SMAD4 forms a complex with SP1 and EP300 at the COL1A2 gene promoter - Homo sapiens
[BlackBoxEvent:R-HSA-9733203] FURIN gene transcription is stimulated by SMAD2/SMAD3:SMAD4 - Homo sapiens
[Reaction:R-HSA-2186643] MEN1 binds SMAD2/3:SMAD4 heterotrimer - Homo sapiens
[Reaction:R-HSA-9736992] p-2S-SMAD2,3:SMAD4 binds JUNB gene promoter - Homo sapiens
[Reaction:R-HSA-8878143] RUNX3 binds SMAD3 and SMAD4 - Homo sapiens
[Reaction:R-HSA-9796225] TEAD2,TEAD4:YAP1, TBXT, FOXH1, and SMAD2,3 bind the FOXA2 gene - Homo sapiens
[Reaction:R-HSA-9823966] EOMES, SMAD2,3, MIXL1 bind the GSC gene - Homo sapiens
[Reaction:R-HSA-9823836] SMAD2,3, FOXA2, TBXT, and GATA6 bind the GATA4 gene - Homo sapiens
[Reaction:R-HSA-9824472] TCF7L2:CTNNB1, EOMES, TBXT, MIXL1, SMAD2,3, FOXA2, GATA4, and GATA6 bind the SOX17 gene - Homo sapiens
[Reaction:R-HSA-9756724] p-2S-SMAD2,3:TRIM33, p-2S-SMAD2,3:SMAD4, CTNNB1, EOMES, and TBPL2 bind FOXH1:MIXL1 gene - Homo sapiens
[Reaction:R-HSA-9733247] YBX1 binds COL1A2 gene promoter - Homo sapiens
[Reaction:R-HSA-9754480] p-2S-SMAD2,3:SMAD4, CTNNB1, and TBPL2 bind FOXH1:SMAD3:EOMES gene - Homo sapiens
[Reaction:R-HSA-9823952] EOMES, SMAD2,3, and GATA6 bind the CXCR4 gene - Homo sapiens
input
[DefinedSet:R-HSA-171175] p-2S-SMAD2,3:SMAD4 [cytosol]
isInDisease
false
isInferred
false
literatureReference
[LiteratureReference:173516] The nuclear import function of Smad2 is masked by SARA and unmasked by TGFbeta-dependent phosphorylation
[LiteratureReference:178148] Transforming growth factor-beta induces nuclear import of Smad3 in an importin-beta1 and Ran-dependent manner
[LiteratureReference:178143] An extended bipartite nuclear localization signal in Smad4 is required for its nuclear import and transcriptional activity
[LiteratureReference:208381] Kinetic analysis of Smad nucleocytoplasmic shuttling reveals a mechanism for transforming growth factor beta-dependent nuclear accumulation of Smads
[LiteratureReference:2584304] Coupling of dephosphorylation and nuclear export of Smads in TGF-beta signaling
[LiteratureReference:2584303] Nucleocytoplasmic shuttling of Smad proteins
maxDepth
1
modified
[InstanceEdit:10867632] Weiser, Joel, 2025年08月27日
name
The SMAD2/3:SMAD4 complex transfers to the nucleus
orthologousEvent
[BlackBoxEvent:R-MMU-173488] The SMAD2/3:SMAD4 complex transfers to the nucleus - Mus musculus
[BlackBoxEvent:R-RNO-173488] The SMAD2/3:SMAD4 complex transfers to the nucleus - Rattus norvegicus
[BlackBoxEvent:R-CFA-173488] The SMAD2/3:SMAD4 complex transfers to the nucleus - Canis familiaris
[BlackBoxEvent:R-BTA-173488] The SMAD2/3:SMAD4 complex transfers to the nucleus - Bos taurus
[BlackBoxEvent:R-SSC-173488] The SMAD2/3:SMAD4 complex transfers to the nucleus - Sus scrofa
[BlackBoxEvent:R-DME-173488] The SMAD2/3:SMAD4 complex transfers to the nucleus - Drosophila melanogaster
[BlackBoxEvent:R-CEL-173488] The SMAD2/3:SMAD4 complex transfers to the nucleus - Caenorhabditis elegans
output
[DefinedSet:R-HSA-173511] p-2S-SMAD2,3:SMAD4 [nucleoplasm]
precedingEvent
[Reaction:R-HSA-170847] Phosphorylated SMAD2 and SMAD3 form a complex with SMAD4 - Homo sapiens
regulatedBy
[NegativeRegulation:9732720] Negative regulation by 'p-T,Y MAPK dimers [cytosol]'
releaseDate
2006年04月24日
reviewStatus
[ReviewStatus:9821382] five stars
reviewed
[InstanceEdit:178196] Heldin, CH, 2006年04月18日 14:26:12
[InstanceEdit:2250308] Huang, Tao, 2012年05月14日
[InstanceEdit:2584311] Chen, Ye-Guang, 2012年11月14日
[InstanceEdit:9773670] Contreras, Osvaldo, 2022年05月02日
schemaClass
BlackBoxEvent
species
[Species:48887] Homo sapiens
stId
R-HSA-173488
summation
[Summation:176008] The phosphorylated R-SMAD:CO-SMAD complex rapidly translocat...
updateTrackers
[UpdateTracker:9788639] Update Tracker - [BlackBoxEvent:173488] The SMAD2/3:SMAD4 complex transfers to the nucleus - v41:[modifyText]
[UpdateTracker:9788231] Update Tracker - [BlackBoxEvent:173488] The SMAD2/3:SMAD4 complex transfers to the nucleus - v43:[addLiteratureReference]
[UpdateTracker:9789229] Update Tracker - [BlackBoxEvent:173488] The SMAD2/3:SMAD4 complex transfers to the nucleus - v38:[modifyText]
[UpdateTracker:9775750] Update Tracker - [BlackBoxEvent:173488] The SMAD2/3:SMAD4 complex transfers to the nucleus - v78:[addRegulator, modifyText]
Referrals
(precedingEvent)
[Reaction:R-HSA-1225919] Phospho R-SMAD(SMAD2,3):CO-SMAD(SMAD4):FOXH1 binds Activin Response Element
[Reaction:R-HSA-1535903] Phospho R-SMAD(SMAD2/3):CO-SMAD(SMAD4):FOXO3 binds FoxO3a-binding elements
[Reaction:R-HSA-9756948] p-2S-SMAD2,3:SMAD4, p-2S-SMAD2,3:TRIM33, CTNNB1, EOMES, and TBPL2 bind FOXH1:SMAD3:GSC gene
[Reaction:R-HSA-9823966] EOMES, SMAD2,3, MIXL1 bind the GSC gene
[Reaction:R-HSA-9823952] EOMES, SMAD2,3, and GATA6 bind the CXCR4 gene
[Reaction:R-HSA-9823836] SMAD2,3, FOXA2, TBXT, and GATA6 bind the GATA4 gene
[Reaction:R-HSA-9824472] TCF7L2:CTNNB1, EOMES, TBXT, MIXL1, SMAD2,3, FOXA2, GATA4, and GATA6 bind the SOX17 gene
[Reaction:R-HSA-9756724] p-2S-SMAD2,3:TRIM33, p-2S-SMAD2,3:SMAD4, CTNNB1, EOMES, and TBPL2 bind FOXH1:MIXL1 gene
[Reaction:R-HSA-9823959] SMAD2,3 and GATA6-AS1 lncRNA bind the GATA6 gene
[Reaction:R-HSA-9823958] EOMES, TBXT (T BRACHYURY), GATA6, and SMAD2,3 bind the FOXA2 gene
[Reaction:R-HSA-870538] TRIM33 (Ectodermin) binds SMAD heterotrimer in the nucleus
[Reaction:R-HSA-173481] SKI/SKIL binds SMAD complex, suppressing TGF-beta signaling
[Reaction:R-HSA-2176475] Phosphorylation of SMAD2 and SMAD3 linker regions by CDK8 or CDK9
[Reaction:R-HSA-2127257] SMAD2/3:SMAD4 heterotrimer forms a complex with RBL1, E2F4/5 and DP1/2
[Reaction:R-HSA-9617996] FOXO1,FOXO3,FOXO4 bind p-2S-SMAD2/3:SMAD4
[Reaction:R-HSA-2187309] SMAD2/3:SMAD4 heterotrimer binds SP1
[Reaction:R-HSA-2186607] TGIF recruits HDAC1 to SMAD2/3:SMAD4 heterotrimer
[Reaction:R-HSA-2187330] PARP1 binds SMAD2/3:SMAD4 heterotrimer
[Reaction:R-HSA-2187388] PPM1A protein phosphatase binds phosphorylated SMAD2/3
[BlackBoxEvent:R-HSA-173545] Ubiquitin-dependent degradation of the SMAD complex terminates TGF-beta signaling
[Reaction:R-HSA-9733207] p-2S-SMAD3:p-2S-SMAD3:SMAD4 forms a complex with SP1 and EP300 at the COL1A2 gene promoter
[BlackBoxEvent:R-HSA-9733203] FURIN gene transcription is stimulated by SMAD2/SMAD3:SMAD4
[Reaction:R-HSA-9733247] YBX1 binds COL1A2 gene promoter
[Reaction:R-HSA-2186643] MEN1 binds SMAD2/3:SMAD4 heterotrimer
[Reaction:R-HSA-9736992] p-2S-SMAD2,3:SMAD4 binds JUNB gene promoter
[Reaction:R-HSA-9754480] p-2S-SMAD2,3:SMAD4, CTNNB1, and TBPL2 bind FOXH1:SMAD3:EOMES gene
[Reaction:R-HSA-8878143] RUNX3 binds SMAD3 and SMAD4
[Reaction:R-HSA-9796225] TEAD2,TEAD4:YAP1, TBXT, FOXH1, and SMAD2,3 bind the FOXA2 gene
(hasEvent)
[Pathway:R-HSA-1502540] Signaling by Activin
[Pathway:R-HSA-1181150] Signaling by NODAL
[Pathway:R-HSA-2173796] SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription
(updatedInstance)
[UpdateTracker:9788639] Update Tracker - [BlackBoxEvent:173488] The SMAD2/3:SMAD4 complex transfers to the nucleus - v41:[modifyText]
[UpdateTracker:9788231] Update Tracker - [BlackBoxEvent:173488] The SMAD2/3:SMAD4 complex transfers to the nucleus - v43:[addLiteratureReference]
[UpdateTracker:9789229] Update Tracker - [BlackBoxEvent:173488] The SMAD2/3:SMAD4 complex transfers to the nucleus - v38:[modifyText]
[UpdateTracker:9775750] Update Tracker - [BlackBoxEvent:173488] The SMAD2/3:SMAD4 complex transfers to the nucleus - v78:[addRegulator, modifyText]
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