SMAD5
SMAD5 (SMAD family member 5, also known as MADH5, JV5-1 and Dwfc) is a transcriptional regulator of the dwarfin/SMAD family that transduces bone morphogenetic protein (BMP) signals. It also has a non-nuclear role in regulating cellular energy metabolism. Browse Assay Genie's current range of SMAD5 research reagents below, or read on for the biology behind the target.
SMAD5 is a transcriptional regulator involved in embryonic development, cell differentiation, angiogenesis and tissue homeostasis. When a BMP ligand binds its receptors at the cell surface, SMAD5 is phosphorylated by activated type I BMP receptors (BMPRIs). It then associates with SMAD4 to form a heteromeric complex that translocates into the nucleus and acts as a transcription factor. This hetero-trimeric complex recognises cis-regulatory elements containing Smad Binding Elements (SBEs) and so modulates the output of the signalling network.
SMAD5 also has a role outside the nucleus. In its non-phosphorylated form it acts in the cytoplasm to regulate energy metabolism, promoting mitochondrial respiration and glycolysis in response to changes in cytoplasmic pH. Mechanistically, it interacts with hexokinase 1 (HK1) and thereby accelerates glycolysis. UniProt lists the protein in the cytoplasm, nucleus and mitochondrion, which fits these dual signalling and metabolic functions. Researchers studying the SMAD5 protein therefore often need to distinguish phosphorylated from non-phosphorylated forms.
The SMAD5 gene belongs to the SMAD family, and the mouse and rat orthologs are both named Smad5. NCBI Gene describes the encoded protein as part of the transforming growth factor beta signalling pathway that inhibits the proliferation of haematopoietic progenitor cells. It is activated by bone morphogenetic protein type 1 receptor kinase and may be involved in cancer. Alternative splicing produces multiple transcript variants. Earlier names for the gene include MAD and mothers against decapentaplegic homolog 5 (Drosophila), reflecting its origin in the Drosophila Mad gene.
SMAD5 is phosphorylated by type I BMP receptors and partners with SMAD4, making it a key readout of BMP pathway activation.
SMAD5 contributes to embryonic development, cell differentiation and angiogenesis, which makes it relevant to studies of tissue formation.
Non-phosphorylated SMAD5 promotes mitochondrial respiration and glycolysis in response to pH changes, partly through interaction with HK1.
SMAD5 is linked to inhibition of haematopoietic progenitor proliferation through TGF-beta signalling and may be involved in cancer.
SMAD5 is a transcriptional regulator in the BMP pathway. After phosphorylation by type I BMP receptors it binds SMAD4, enters the nucleus and regulates genes through Smad Binding Elements. Non-phosphorylated SMAD5 also promotes mitochondrial respiration and glycolysis in the cytoplasm, partly by interacting with HK1.
SMAD5 is also called MADH5, JV5-1 and Dwfc. Earlier names include MAD and SMAD, mothers against DPP homolog 5 (Drosophila). The HGNC full name is SMAD family member 5. NCBI Gene notes that alternative splicing gives multiple transcript variants.
Mouse and rat both have a Smad5 ortholog. The name derives from the Drosophila Mad gene. NCBI Gene says SMAD5 may be involved in cancer, and check the datasheet of any product for its validated reactivity.
Other SMAD family members, including receptor-regulated, common-partner and inhibitory SMADs involved in BMP and TGF-beta signalling.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q99717; product specifications from Assay Genie datasheets.