SMAD1

Description

The SMAD1 (SMAD family member 1) is a protein-coding gene located on chromosome 4.

Mothers against decapentaplegic homolog 1, also known as SMAD family member 1 or SMAD1, is a protein that in humans is encoded by the SMAD1 gene. SMAD1 belongs to the SMAD, a family of proteins similar to the gene products of the Drosophila gene 'mothers against decapentaplegic' (Mad) and the C. elegans gene Sma. The name is a combination of the two; and based on a tradition of such unusual naming within the gene research community. It was found that a mutation in the 'Drosophila' gene, MAD, in the mother, repressed the gene, decapentaplegic, in the embryo. Mad mutations can be placed in an allelic series based on the relative severity of the maternal effect enhancement of weak dpp alleles, thus explaining the name Mothers against dpp. SMAD proteins are signal transducers and transcriptional modulators that mediate multiple signaling pathways. This protein mediates the signals of the bone morphogenetic proteins (BMPs), which are involved in a range of biological activities including cell growth, apoptosis, morphogenesis, development and immune responses. In response to BMP ligands, this protein can be phosphorylated and activated by the BMP receptor kinase. The phosphorylated form of this protein forms a complex with SMAD4, which is important for its function in the transcription regulation. This protein is a target for SMAD-specific E3 ubiquitin ligases, such as SMURF1 and SMURF2, and undergoes ubiquitination and proteasome-mediated degradation.

SMAD1 acts as a transcriptional modulator, playing a crucial role in various cellular processes including embryonic development, cell differentiation, and tissue homeostasis. Upon binding of BMP ligands to their receptors at the cell surface, SMAD1 is phosphorylated by activated type I BMP receptors (BMPRIs). The phosphorylated SMAD1 then associates with SMAD4, forming a hetero-trimeric complex that translocates into the nucleus and functions as a transcription factor. This complex recognizes specific cis-regulatory elements containing Smad Binding Elements (SBEs) to modulate the signaling network. Furthermore, the SMAD1/OAZ1/PSMB4 complex mediates the degradation of the CREBBP/EP300 repressor SNIP1. SMAD1 also positively regulates BMP4-induced expression of the odontogenic development regulator MSX1 following IPO7-mediated nuclear import.

SMAD1 is also known as BSP-1, BSP1, JV4-1, JV41, MADH1, MADR1.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing