Recombinant Human Smad3 protein

Specifications

Form

Liquid

Additional notes

ab89353 is purified using conventional chromatography techniques.

General info

Function

SMAD3 is a receptor-regulated SMAD that functions as an intracellular signal transducer and transcriptional modulator, activated by TGF-beta and activin type 1 receptor kinases. It binds to the TRE element in promoters of numerous genes regulated by TGF-beta, and upon forming a complex with SMAD4, activates transcription. Additionally, SMAD3 can form a complex with SMAD4, JUN, and FOS at the AP-1/SMAD site to regulate TGF-beta-mediated transcription. SMAD3 may inhibit wound healing by modulating the growth and migration of primary keratinocytes and altering TGF-beta-mediated monocyte chemotaxis, with this effect being potentially hormone-sensitive. Furthermore, SMAD3 is involved in regulating chondrogenesis and osteogenesis and may inhibit early bone fracture healing. It also positively regulates PDPK1 kinase activity by promoting its dissociation from the 14-3-3 protein YWHAQ, which negatively regulates it. This supplementary information is collated from multiple sources and compiled automatically.

Sequence similarities

Belongs to the dwarfin/SMAD family.

Post-translational modifications

Phosphorylated on serine and threonine residues. Enhanced phosphorylation in the linker region on Thr-179, Ser-204 and Ser-208 on EGF and TGF-beta treatment. Ser-208 is the main site of MAPK-mediated phosphorylation. CDK-mediated phosphorylation occurs in a cell-cycle dependent manner and inhibits both the transcriptional activity and antiproliferative functions of SMAD3. This phosphorylation is inhibited by flavopiridol. Maximum phosphorylation at the G(1)/S junction. Also phosphorylated on serine residues in the C-terminal SXS motif by TGFBR1 and ACVR1. TGFBR1-mediated phosphorylation at these C-terminal sites is required for interaction with SMAD4, nuclear location and transactivational activity, and appears to be a prerequisite for the TGF-beta mediated phosphorylation in the linker region. Dephosphorylated in the C-terminal SXS motif by PPM1A. This dephosphorylation disrupts the interaction with SMAD4, promotes nuclear export and terminates TGF-beta-mediated signaling. Phosphorylation at Ser-418 by CSNK1G2/CK1 promotes ligand-dependent ubiquitination and subsequent proteasome degradation, thus inhibiting SMAD3-mediated TGF-beta responses. Phosphorylated by PDPK1.. Acetylation in the nucleus by EP300 in the MH2 domain regulates positively its transcriptional activity and is enhanced by TGF-beta.. Poly-ADP-ribosylated by PARP1 and PARP2. ADP-ribosylation negatively regulates SMAD3 transcriptional responses during the course of TGF-beta signaling.. Ubiquitinated. Monoubiquitinated, leading to prevent DNA-binding (PubMed:21947082). Deubiquitination by USP15 alleviates inhibition and promotes activation of TGF-beta target genes (PubMed:21947082). Ubiquitinated by RNF111, leading to its degradation: only SMAD3 proteins that are 'in use' are targeted by RNF111, RNF111 playing a key role in activating SMAD3 and regulating its turnover (By similarity). Undergoes STUB1-mediated ubiquitination and degradation (PubMed:24613385).

Subcellular localisation

Nucleus