R-SMAD

R-SMADs are receptor-regulated SMADs. SMADs are transcription factors that transduce extracellular TGF-β superfamily ligand signaling from cell membrane bound TGF-β receptors into the nucleus where they activate transcription TGF-β target genes. R-SMADS are directly phosphorylated on their c-terminus by type 1 TGF-β receptors through their intracellular kinase domain, leading to r-SMAD activation.

R-SMADS include SMAD2 and SMAD3 from the TGF-β/Activin/Nodal branch, and SMAD1, SMAD5 and SMAD8 from the BMP/GDP branch of TGF-β signaling.

In response to signals by the TGF-β superfamily of ligands these proteins associate with receptor kinases and are phosphorylated at an SSXS motif at their extreme C-terminus. These proteins then typically bind to the common mediator Smad or co-SMAD SMAD4.

Smad complexes then accumulate in the cell nucleus where they regulate transcription of specific target genes:

SMAD

SMAD may refer to:

SMAD (protein)

SMADs are intracellular proteins that transduce extracellular signals from transforming growth factor beta ligands to the nucleus where they activate downstream gene transcription.

The SMADs, which form a trimer of two receptor-regulated SMADs and one co-SMAD, act as transcription factors that regulate the expression of certain genes.

Classes

There are three classes of SMAD:

Nomenclature

The SMAD proteins are homologs of both the Drosophila protein, mothers against decapentaplegic (MAD) and the Caenorhabditis elegans protein SMA (from gene sma for small body size). The name is a portmanteau of the two. 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.

Mothers against decapentaplegic homolog 7

Mothers against decapentaplegic homolog 7 or SMAD7 is a protein that in humans is encoded by the SMAD7 gene.

SMAD7 is a protein that, as its name describes, is a homolog of the Drosophila gene: "Mothers against decapentaplegic". It belongs to the SMAD family of proteins, which belong to the TGFβ superfamily of ligands. Like many other TGFβ family members, SMAD7 is involved in cell signalling. It is a TGFβ type 1 receptor antagonist. It blocks TGFβ1 and activin associating with the receptor, blocking access to SMAD2. It is an inhibitory SMAD (I-SMAD) and is enhanced by SMURF2.

Smad7 enhances muscle differentiation.

Structure

Smads proteins contain two conserved domains. The Mad Homology domain 1 (MH1 domain) is at the N-terminal and the Mad Homology domain 2 (MH2 domain) is at the C-terminal. Between them there is a linker region which is full of regulatory sites. The MH1 domain has DNA binding activity while the MH2 domain has transcriptional activity. The linker region contains important regulatory peptide motifs including potential phosphorylation sites for mitogen-activated protein kinases(MAPKs), Erk-family MAP kinases, the Ca2+ /calmodulin-dependent protein kinase II (CamKII) and protein kinase C (PKC). Smad7 do not have the MH1 domain. A proline-tyrosine (PY) motif presents at its linker region enables its interaction with the WW domains of the E3 ubiquitin ligase, the Smad ubiquitination-related factors (Smurf2). It resides predominantly in the nucleus at basal state and translocates to the cytoplasm by TGF-β stimulation.