Mh1 domain of Smad is a degraded homing endonuclease

J Mol Biol. 2001 Mar 16;307(1):31-7. doi: 10.1006/jmbi.2000.4486.


Smad proteins are eukarytic transcription regulators in the TGF-beta signaling cascade. Using a combination of sequence and structure-based analyses, we argue that MH1 domain of Smad is homologous to the diverse His-Me finger endonuclease family enzymes. The similarity is particularly extensive with the I-PpoI endonuclease. In addition to the global fold similarities, both proteins possess a conserved motif of three cysteine residues and one histidine residue which form a zinc-binding site in I-PpoI. Sequence and structure conservation in the motif region strongly suggest that MH1 domain may also incorporate a metal ion in its structural core. MH1 of Smad3 and I-PpoI exhibit similar nucleic acid binding mode and interact with DNA major groove through an antiparallel beta-sheet. MH1 is an example of transcription regulator derived from the ancient enzymatic domain that lost its catalytic activity but retained DNA-binding sites.

MeSH terms

  • Amino Acid Sequence
  • Catalytic Domain
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / metabolism
  • Endodeoxyribonucleases / chemistry*
  • Endodeoxyribonucleases / metabolism
  • Humans
  • Models, Molecular
  • Protein Folding
  • Protein Structure, Tertiary
  • Sequence Homology, Amino Acid
  • Smad Proteins
  • Smad3 Protein
  • Trans-Activators / chemistry*
  • Trans-Activators / metabolism
  • Zinc / metabolism


  • DNA-Binding Proteins
  • SMAD3 protein, human
  • Smad Proteins
  • Smad3 Protein
  • Trans-Activators
  • Endodeoxyribonucleases
  • I-Ppo endonuclease
  • Zinc