SMAD5

Transcriptional regulator that plays a role in various cellular processes including embryonic development, cell differentiation, angiogenesis and tissue homeostasis (PubMed:12064918, PubMed:16516194). Upon BMP ligand binding to their receptors at the cell surface, is phosphorylated by activated type I BMP receptors (BMPRIs) and associates with SMAD4 to form a heteromeric complex which translocates into the nucleus acting as transcription factor (PubMed:9442019). In turn, the hetero-trimeric complex recognizes cis-regulatory elements containing Smad Binding Elements (SBEs) to modulate the outcome of the signaling network (PubMed:33510867). Non-phosphorylated SMAD5 has a cytoplasmic role in energy metabolism regulation by promoting mitochondrial respiration and glycolysis in response to cytoplasmic pH changes (PubMed:28675158). Mechanistically, interacts with hexokinase 1/HK1 and thereby accelerates glycolysis (PubMed:28675158).

Phosphorylated on serine by BMP (bone morphogenetic proteins) type 1 receptor kinase.

Ubiquitin-mediated proteolysis by SMAD-specific E3 ubiquitin ligase SMURF1.

Belongs to the dwarfin/SMAD family.

Ubiquitous.

• Cytoplasm
• Nucleus
• Mitochondrion
• Cytoplasmic in the absence of ligand. Migrates to the nucleus when complexed with SMAD4.

MADH5, SMAD5, Mothers against decapentaplegic homolog 5, MAD homolog 5, Mothers against DPP homolog 5, JV5-1, SMAD family member 5, SMAD 5, Smad5, hSmad5

• entrezGene:4086
• entrezGene:4090
• omim:603110
• omim:601595
• swissprot:Q99717
• swissprot:Q15797

Proteins

Epigenetics

• Oncology

52258Da