Diverse membrane-associated proteins contain a novel SMP domain.
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.
Lee
Ian
I
Computational Molecular Biology Programme, Institute of Molecular and Cell Biology, Proteos, Singapore. leehh@imcb.a-star.edu.sg
Hong
Wanjin
W
D000595:Amino Acid Sequence; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000378:metabolism; D018832:Molecular Chaperones / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary
D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones