SMURF2 monoubiquitinates SMAD3

Stable Identifier
Reaction [transition]
Homo sapiens
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

SMURF2 monoubiquitinates SMAD3 on lysine residues in the MH2 domain. Lysines K333 and K378 are likely the major sites for monoubiquitination. Lysine K409 is also monoubiquitinated, and possibly lysine K341. Since lysines K333 and K378 are predicted to stabilize the interaction of SMAD3 with SMAD4, monoubiquitination of these lysine residues is expected to disrupt SMAD2/3:SMAD4 heterotrimer. SMURF2-mediated disruption of endogenous Smad2/3:Smad4 heterotrimers was demonstrated in mouse embryonic fibroblasts. SMURF2 also ubiquitinates SMAD2 phosphorylated in the linker region, but loss of Smurf2 has less impact on Smad2 ubiquitination than on Smad3 in vivo.

Literature References
PubMed ID Title Journal Year
22045334 Ablation of Smurf2 reveals an inhibition in TGF-? signalling through multiple mono-ubiquitination of Smad3

Zhang, YE, Coussens, NP, Tang, LY, Li, C, Tang, Y, Deng, CX, Yamashita, M, Cheng, SY, Wang, X

EMBO J 2011
Catalyst Activity

ubiquitin-protein transferase activity of p-T-2S-SMAD2,3:SMAD4:SMURF2 [nucleoplasm]

Orthologous Events
Cite Us!