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Protein Domain : IPR013019

Name  MAD homology, MH1 Short Name  MAD_homology_MH1
Type  Domain Description  Smad proteins are signal transducers and transcriptional comodulators of the TGF-beta superfamily of ligands, which play a central role in regulating a broad range of cellular responses, including cell growth, differentiation, and specification of developmental fate, in diverse organisms from Caenorhabditis elegansto humans. Ligand binding to specific transmembrane receptor kinases induces receptor oligomerisation and phosphorylation of the receptor specific Smad protein (R-Smad) in the cytoplasm. The R-Smad proteins regulate distinct signalling pathways. Smad1, 5 and 8 mediate the signals of bone morphogenetic proteins (BMPs), while Smad2 and 3 mediate the signals of activins and TGF-betas. Upon ligand stimulation, R-Smad proteins are phosphorylated at the conserved C-terminal tail sequence, SS*xS* (where S* denotes a site of phosphorylation). The phosphorylated states of R-Smad proteins form heteromeric complexes with Smad4 and are translocated into the nucleus. In the nucleus, the heteromeric complexes function as gene-specific transcription activators by binding to promoters and interacting with transcriptional coactivators. Smad6 and Smad7 are inhibitory Smad proteins that inhibit TGF-beta signalling by interfering with either receptor-mediated phosphorylation or hetero-oligomerisation between Smad4 and R-Smad proteins. Smad proteins comprise two conserved MAD homology domains, one in the N terminus (MH1) and one in the C terminus (MH2), separated by a more variable, proline-rich linker region. The MH1 domain has a role in DNA binding and negatively regulates the functions of MH2 domain, whereas the MH2 domain is responsible for transactivation and mediates phosphorylation-triggered heteromeric assembly between Smad4 and R-Smad [, ]. The MH1 domain adopts a compact globular fold, with four alpha helices, six short beta strands, and five loops. The N-terminal half of the sequence consists of three alpha helices, and the C-terminal half contains all six beta strands, which form two small beta sheets and one beta hairpin. The fourth alpha helix is located in the hydrophobic core of the molecule, surrounded by the N-terminal three alpha helices on one side and by the two small beta sheets and the beta hairpin on the other side. These secondary structural elements are connected with five intervening surface loops. The MH1 domain employs a novel DNA-binding motif, an 11-residue beta-hairpin formed by strands B2 and B3, to contact DNA in the major groove. Two residues in the L3 loop and immediately preceding strand B2 also contribute significantly to DNA recognition. The beta hairpin appears to protrude outward from the globular MH1 core [].

Publication Counts Displayer

0 Child Features

0 Contains

3 Cross References

Identifier
Source . Name

Subject . Primary Identifier
PS51075 PROFILE IPR013019
G3DSA:3.90.520.10 GENE3D IPR013019
SSF56366 SSF IPR013019

3 Data Sets

Name URL
TrEMBL data set http://www.ebi.ac.uk/trembl/
InterPro data set  
InterPro GO Annotation data set  

1 Found In

DB identifier Name Short Name Type
IPR013790 Dwarfin Dwarfin Family

5 GO Annotation


Subject . Secondary Identifier

Subject . Name

Subject . Symbol

Ontology Term . Identifier

Ontology Term . Name
MAD homology, MH1   GO:0003700 sequence-specific DNA binding transcription factor activity
MAD homology, MH1   GO:0006355 regulation of transcription, DNA-templated
MAD homology, MH1   GO:0007179 transforming growth factor beta receptor signaling pathway
MAD homology, MH1   GO:0005622 intracellular
MAD homology, MH1   GO:0005667 transcription factor complex

5 Ontology Annotations


Subject . Secondary Identifier

Subject . Name

Subject . Symbol

Ontology Term . Identifier

Ontology Term . Name
MAD homology, MH1   GO:0003700 sequence-specific DNA binding transcription factor activity
MAD homology, MH1   GO:0006355 regulation of transcription, DNA-templated
MAD homology, MH1   GO:0007179 transforming growth factor beta receptor signaling pathway
MAD homology, MH1   GO:0005622 intracellular
MAD homology, MH1   GO:0005667 transcription factor complex

1 Parent Features

DB identifier Name Short Name Type
IPR003619 MAD homology 1, Dwarfin-type MAD_homology1_Dwarfin-type Domain

63 Proteins

DB identifier Primary Accession
Organism . Name
FBpp0099512 Q5U110 Drosophila melanogaster
FBpp0085176 O62609 Drosophila melanogaster
FBpp0085177 Q8IMG6 Drosophila melanogaster
FBpp0077302 P42003 Drosophila melanogaster
FBpp0071140 O96660 Drosophila melanogaster
FBpp0304648 M9PBX0 Drosophila melanogaster
FBpp0297040 I5AND6 Drosophila pseudoobscura
FBpp0297039 Q29AF0 Drosophila pseudoobscura
FBpp0282725 Q29HD9 Drosophila pseudoobscura
FBpp0284200 Q297H8 Drosophila pseudoobscura
FBpp0287731 B5DJI3 Drosophila pseudoobscura
FBpp0163632 B4L8H6 Drosophila mojavensis
FBpp0167198 B4KEV0 Drosophila mojavensis
FBpp0172617 B4K7Y4 Drosophila mojavensis
FBpp0173071 B4KC87 Drosophila mojavensis
FBpp0224986 B4M5J3 Drosophila virilis
FBpp0233179 B4M1Z3 Drosophila virilis
FBpp0233970 B4LU30 Drosophila virilis
FBpp0237509 B4M0Z7 Drosophila virilis
FBpp0255962 B4PNF5 Drosophila yakuba
FBpp0259945 B4NXE4 Drosophila yakuba
FBpp0262489 B4Q0M2 Drosophila yakuba
FBpp0269616 B4PM83 Drosophila yakuba
A8XPG1_CAEBR A8XPG1 Caenorhabditis briggsae
A8X5U1_CAEBR A8X5U1 Caenorhabditis briggsae
A8X7T9_CAEBR A8X7T9 Caenorhabditis briggsae
A8XFY2_CAEBR A8XFY2 Caenorhabditis briggsae
A8WS81_CAEBR A8WS81 Caenorhabditis briggsae
H2W3N7_CAEJA H2W3N7 Caenorhabditis japonica
K7H4A8_CAEJA K7H4A8 Caenorhabditis japonica