Diverse membrane-associated proteins contain a novel SMP domain

FASEB J. 2006 Feb;20(2):202-6. doi: 10.1096/fj.05-4581hyp.


We have analyzed the sequence of a mitochondrial integral membrane protein, Mdm12, and found that it forms the prototype for a novel domain, designated the SMP domain, that is common to an extended family of membrane-associated proteins. Comprehensive sequence searches using protein alignment models of SMP proteins were cross-validated by statistical resampling; providing strong support for these relationships. No consensus of 3-dimensional structure was reached upon threading sequences through known folds. SMP proteins are widespread amongst eukaryotic species with a particular enrichment in plants and features suggestive of species-specific functional variations. Members of 2 SMP families, the mitochore and tricalbin proteins, are essential components of protein complexes involved in mitochondrial inheritance and receptor endocytosis while a third SMP protein family, HT008, is associated with the Rvs161-Rvs167 complex, a known regulator of sphingolipid metabolism. In addition, HT008 and PDZK8 SMP proteins possess additional protein-protein interaction domains in domain architectures that are typical of protein scaffolds and adaptors. We therefore predict that the SMP domain is an important link between these distinct membrane-associated proteins and a key regulatory hub for unidentified global regulators.-Lee, I., Hong, W. Diverse membrane-associated proteins contain a novel SMP domain.

MeSH terms

  • Amino Acid Sequence
  • Membrane Proteins / chemistry*
  • Membrane Proteins / metabolism*
  • Mitochondrial Membranes / metabolism
  • Mitochondrial Proteins / chemistry
  • Mitochondrial Proteins / metabolism
  • Molecular Chaperones / chemistry
  • Molecular Chaperones / metabolism
  • Molecular Sequence Data
  • Protein Structure, Tertiary


  • Membrane Proteins
  • Mitochondrial Proteins
  • Molecular Chaperones