Reactome | Phosphorylated SMAD2 and SMAD3 form a complex with SMAD4

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Phosphorylated SMAD2 and SMAD3 form a complex with SMAD4 Show undefined attributes

authored	[InstanceEdit:171270] Heldin, CH, Moustakas, A, Huminiecki, L, Jassal, B, 2006-02-02
category	transition
compartment	[Compartment:70101] cytosol
created	[InstanceEdit:170836] Jassal, B, 2006-01-18 10:19:52
dbId	170847
diseaseReaction	[FailedReaction:R-HSA-3311014] SMAD4 MH2 Domain Mutants do not bind phosphorylated SMAD2 and SMAD3 - Homo sapiens [FailedReaction:R-HSA-3315483] Phosphorylated SMAD2/3 MH2 Domain Mutants do not bind SMAD4 - Homo sapiens
displayName	Phosphorylated SMAD2 and SMAD3 form a complex with SMAD4
edited	[InstanceEdit:170836] Jassal, B, 2006-01-18 10:19:52 [InstanceEdit:2187413] Jassal, B, 2012-04-10 [InstanceEdit:9773750] Orlic-Milacic, Marija, 2022-05-09
eventOf	[Pathway:R-HSA-2173796] SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription - Homo sapiens [Pathway:R-HSA-1181150] Signaling by NODAL - Homo sapiens [Pathway:R-HSA-2173789] TGF-beta receptor signaling activates SMADs - Homo sapiens
followingEvent	[Reaction:R-HSA-2031355] WWTR1 binds SMAD2/3:SMAD4 heterotrimer - Homo sapiens [BlackBoxEvent:R-HSA-173488] The SMAD2/3:SMAD4 complex transfers to the nucleus - Homo sapiens
input	3 × [DefinedSet:R-HSA-171182] p-2S-SMAD2,3 [cytosol] 3 × [EntityWithAccessionedSequence:R-HSA-170862] SMAD4 [cytosol]
isInDisease	false
isInferred	false
literatureReference	[LiteratureReference:175954] TGF-beta receptor-mediated signalling through Smad2, Smad3 and Smad4 [LiteratureReference:1225903] Smad proteins exist as monomers in vivo and undergo homo- and hetero-oligomerization upon activation by serine/threonine kinase receptors [LiteratureReference:202606] Structural basis of Smad1 activation by receptor kinase phosphorylation [LiteratureReference:208376] Structural basis of heteromeric smad protein assembly in TGF-beta signaling [LiteratureReference:208162] Crystal structure of a phosphorylated Smad2. Recognition of phosphoserine by the MH2 domain and insights on Smad function in TGF-beta signaling. [LiteratureReference:3009206] Endofin, a FYVE domain protein, interacts with Smad4 and facilitates transforming growth factor-beta signaling
maxDepth	1
modified	[InstanceEdit:10914110] Weiser, Joel, 2026-03-16
name	Phosphorylated SMAD2 and SMAD3 form a complex with SMAD4
negativePrecedingEvent	[NegativePrecedingEvent:9754412] Futile Cycle: USP9X (FAM) deubiquitinates SMAD4
orthologousEvent	[Reaction:R-MMU-170847] Phosphorylated SMAD2 and SMAD3 form a complex with SMAD4 - Mus musculus [Reaction:R-RNO-170847] Phosphorylated SMAD2 and SMAD3 form a complex with SMAD4 - Rattus norvegicus [Reaction:R-CFA-170847] Phosphorylated SMAD2 and SMAD3 form a complex with SMAD4 - Canis familiaris [Reaction:R-BTA-170847] Phosphorylated SMAD2 and SMAD3 form a complex with SMAD4 - Bos taurus [Reaction:R-SSC-170847] Phosphorylated SMAD2 and SMAD3 form a complex with SMAD4 - Sus scrofa [Reaction:R-XTR-170847] Phosphorylated SMAD2 and SMAD3 form a complex with SMAD4 - Xenopus tropicalis [Reaction:R-GGA-170847] Phosphorylated SMAD2 and SMAD3 form a complex with SMAD4 - Gallus gallus [Reaction:R-DME-170847] Phosphorylated SMAD2 and SMAD3 form a complex with SMAD4 - Drosophila melanogaster [Reaction:R-CEL-170847] Phosphorylated SMAD2 and SMAD3 form a complex with SMAD4 - Caenorhabditis elegans
output	[DefinedSet:R-HSA-171175] p-2S-SMAD2,3:SMAD4 [cytosol]
precedingEvent	[Reaction:R-HSA-170850] Phosphorylated SMAD2/3 dissociates from TGFBR - Homo sapiens [Reaction:R-HSA-1181355] Phosphorylation of R-SMAD2/3 by NODAL receptor - Homo sapiens [Reaction:R-HSA-1549526] Phosphorylation of SMAD2,3 by Activin:Activin Receptor - Homo sapiens
releaseDate	2006-04-24
reviewStatus	[ReviewStatus:9821382] five stars
reviewed	[InstanceEdit:178196] Heldin, CH, 2006-04-18 14:26:12 [InstanceEdit:2250308] Huang, Tao, 2012-05-14 [InstanceEdit:2584311] Chen, Ye-Guang, 2012-11-14 [InstanceEdit:9773670] Contreras, Osvaldo, 2022-05-02
revised	[InstanceEdit:2186595] Orlic-Milacic, M, 2012-04-04 [InstanceEdit:3009218] Orlic-Milacic, M, 2013-02-04
schemaClass	Reaction
species	[Species:48887] Homo sapiens
stId	R-HSA-170847
summation	[Summation:176014] The phosphorylated C-terminal tail of R-SMAD induces a confo...
updateTrackers	[UpdateTracker:9775664] Update Tracker - [Reaction:170847] Phosphorylated SMAD2 and SMAD3 form a complex with SMAD4 - v78:[modifyText] [UpdateTracker:9788018] Update Tracker - [Reaction:170847] Phosphorylated SMAD2 and SMAD3 form a complex with SMAD4 - v44:[addLiteratureReference, modifyText] [UpdateTracker:9788685] Update Tracker - [Reaction:170847] Phosphorylated SMAD2 and SMAD3 form a complex with SMAD4 - v41:[addLiteratureReference, modifyText] [UpdateTracker:9792168] Update Tracker - [Reaction:170847] Phosphorylated SMAD2 and SMAD3 form a complex with SMAD4 - v23:[modifyText] [UpdateTracker:9789181] Update Tracker - [Reaction:170847] Phosphorylated SMAD2 and SMAD3 form a complex with SMAD4 - v38:[addLiteratureReference, modifyText] [UpdateTracker:9788233] Update Tracker - [Reaction:170847] Phosphorylated SMAD2 and SMAD3 form a complex with SMAD4 - v43:[addLiteratureReference] [UpdateTracker:9789860] Update Tracker - [Reaction:170847] Phosphorylated SMAD2 and SMAD3 form a complex with SMAD4 - v37:[addLiteratureReference]

Referrals

(precedingEvent)	[Reaction:R-HSA-2031355] WWTR1 binds SMAD2/3:SMAD4 heterotrimer [BlackBoxEvent:R-HSA-173488] The SMAD2/3:SMAD4 complex transfers to the nucleus
(hasEvent)	[Pathway:R-HSA-2173796] SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription [Pathway:R-HSA-2173789] TGF-beta receptor signaling activates SMADs [Pathway:R-HSA-1181150] Signaling by NODAL [Pathway:R-HSA-1502540] Signaling by Activin
(normalReaction)	[FailedReaction:R-HSA-3311014] SMAD4 MH2 Domain Mutants do not bind phosphorylated SMAD2 and SMAD3 [FailedReaction:R-HSA-3315483] Phosphorylated SMAD2/3 MH2 Domain Mutants do not bind SMAD4
(updatedInstance)	[UpdateTracker:9775664] Update Tracker - [Reaction:170847] Phosphorylated SMAD2 and SMAD3 form a complex with SMAD4 - v78:[modifyText] [UpdateTracker:9788018] Update Tracker - [Reaction:170847] Phosphorylated SMAD2 and SMAD3 form a complex with SMAD4 - v44:[addLiteratureReference, modifyText] [UpdateTracker:9788685] Update Tracker - [Reaction:170847] Phosphorylated SMAD2 and SMAD3 form a complex with SMAD4 - v41:[addLiteratureReference, modifyText] [UpdateTracker:9792168] Update Tracker - [Reaction:170847] Phosphorylated SMAD2 and SMAD3 form a complex with SMAD4 - v23:[modifyText] [UpdateTracker:9789181] Update Tracker - [Reaction:170847] Phosphorylated SMAD2 and SMAD3 form a complex with SMAD4 - v38:[addLiteratureReference, modifyText] [UpdateTracker:9788233] Update Tracker - [Reaction:170847] Phosphorylated SMAD2 and SMAD3 form a complex with SMAD4 - v43:[addLiteratureReference] [UpdateTracker:9789860] Update Tracker - [Reaction:170847] Phosphorylated SMAD2 and SMAD3 form a complex with SMAD4 - v37:[addLiteratureReference]

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