Multidimensional Drift of Sequence Attributes and Functional Profiles in the Superfamily of the Three-Finger Proteins and Their Structural Homologues.

Functional diversity of the three-finger-protein domain (TFPD) had been acquired via hypervariability of some sequence positions and extensive insertion/deletion of short AA-segments that caused multidimensional drift of several sequence attributes such as the overall (HI) and local hydrophobicity levels, the isoelectric point (pI), distribution of charges, and local polarizability potentials. In consequence, the pIs of various TFPDs vary from 3 to 10, and the HIs span from highly hydrophilic to extreme hydrophobic levels. Our analyses of diverse genomic databases suggest that a primordial TFP-like fold could have been adapted to extracellular N-terminal domain (ECD) of the TGFβ series of receptors that are crucial for morphogenesis of multicellular organisms with elaborated body plans. It seems plausible that from the exons coding for the primordial ECD had radiated some ORFs that gave rise to small monodomain and multidomain TFPs that may be either membrane-bound or soluble entities and whose repertoire expanded in the genomes of vertebrates. We show that the above-mentioned attributes have been restrained within narrow ranges in several functionally related groups of TFPs that are expressed in miscellaneous organisms.