SMAD domain
IPR001132
Definition
This entry represents the SMAD (Mothers against decapentaplegic (MAD) homologue) (also called MH2 for MAD homology 2) domain found at the C-terminal of MAD related proteins such as Smads. This domain is separated from the MH1 domain by a non-conserved linker region. The MH2 domain mediates interaction with a wide variety of proteins and provides specificity and selectivity to Smad function and also is critical for mediating interactions in Smad oligomers. Unlike MH1, MH2 does not bind DNA. The well-studied MH2 domain of Smad4 is composed of five α helices and three loops enclosing a β sandwich [[cite:PMID:8799132], [cite:PMID:9230443], [cite:PMID:11532220]]. Receptor-regulated SMAD (R-SMAD) proteins, also known as mammalian dwarfins, are intracellular signal transducers and transcriptional modulators that are phosphorylated in response to transforming growth factor-beta (TGF-β) and activin type I receptor kinases and are implicated in the control of cell growth. They bind TGF-β response elements (TREs) in the promoter regions of many TGF-β-regulated genes and, upon formation of SMAD2/SMAD4 complexes, activate transcription, including TGFB1-mediated induction of odontoblastic differentiation genes in dental papilla cells (by similarity). In addition, R-SMADs positively regulate PDPK1 kinase activity by promoting its dissociation from the inhibitory 14-3-3 protein YWHAQ and may act as tumour suppressors in colorectal carcinoma PMID:14631647. The mammalian dwarfin/SMAD family also includes the Drosophila protein MAD, which is required for the function of decapentaplegic (DPP) and participates in DPP signalling; Drosophila Mad binds DNA and directly mediates activation of vestigial by Dpp [[cite:PMID:8799132], [cite:PMID:19218245]]. A related SMAD domain is also present in nuclear factor I (NF-I), also known as CCAAT box-binding transcription factor (CTF) [[cite:PMID:9230443], [cite:PMID:17507407]].
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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