Diverse membrane‐associated proteins contain a novel SMP domain

ABSTRACT 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. FASEB J. 20, 202–206 (2006)