Transcriptional regulator that plays a role in various cellular processes including embryonic development, cell differentiation, angiogenesis and tissue homeostasis (, ). 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 an heteromeric complex which translocates into the nucleus acting as transcription factor . In turn, the hetero-trimeric complex recognizes cis-regulatory elements containing Smad Binding Elements (SBEs) to modulate the outcome of the signaling network . Non-phosphorylated SMAD5 has a cytoplasmic role in energy metabolism regulation by promoting mitochondrial respiration and glycolysis in response to cytoplasmic pH changes . Mechanistically, interacts with hexokinase 1/HK1 and thereby accelerates glycolysis .
Subcellular locations: Cytoplasm, Nucleus, Mitochondrion
Cytoplasmic in the absence of ligand. Migrates to the nucleus when complexed with SMAD4.
Ubiquitous.