MAD homology, MH1
IPR013019
Definition
This entry represents a MAD homology 1 (MH1) domain in the N-terminal region of Smad proteins (mH1). Smad proteins are signal transducers and transcriptional comodulators of TGF-beta superfamily ligands, which regulate key cellular processes such as proliferation, differentiation, and developmental fate. Ligand binding to transmembrane receptor kinases induces receptor oligomerisation and phosphorylation of receptor-regulated Smads (R-Smads), including Smad1, Smad5, and Smad8 for BMP signalling, and Smad2 and Smad3 for activin and TGF-beta signalling. Phosphorylated R-Smads form heteromeric complexes with Smad4 that accumulate in the nucleus and act as gene-specific transcription factors, while inhibitory Smads (Smad6 and Smad7) antagonise this pathway. Smad proteins contain two conserved MAD homology domains, one in the N-terminal region (MH1) and one in the C-terminal region (MH2), separated by a proline-rich linker; the MH1 domain mediates DNA binding and negatively regulates MH2, whereas the C-terminal MH2 domain mediates transactivation and phosphorylation-dependent complex assembly with Smad4 and R-Smads. [[cite:PMID:9741623], [cite:PMID:11779503]].
8 human proteins with this domain
Each is a reviewed human protein in the Seroatlas serome and a potential autoantibody target; this domain groups them into one antibody-relevant category. Every entry links to its own record.
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