Classification and evolution of EF-hand proteins

Forty-five distinct subfamilies of EF-hand proteins have been identified. T hey contain from two to eight EF-hands that are recognizable by amino acid sequence as being statistically similar to other EF-hand domains. All prote ins within one subfamily are congruent to one another, i.e. the dendrogram computed from one of the EF-hand domains is similar,,within statistical err or, to the dendrogram computed from another(s) domain. Thirteen subfamilies - including Calmodulin, Troponin C, Essential light chain, Regulatory ligh t chain - referred to collectively as CTER, are congruent with one another. They appear to have evolved from a single ur-domain by two cycles of gene duplication and fusion, The subfamilies of CTER subsequently evolved by gen e duplications and speciations. The remaining 32 subfamilies do not show su ch general patterns of congruence; however, some - such as S100, intestinal calcium binding protein (calbindin 9kd), and trichohylin - do not form con gruent clusters of subfamilies. Nearly all of the domains 1, 3, 5, and 7 ar e most similar to other ODD domains. Correspondingly the EVEN numbered doma ins of all 45 subfamilies most closely resemble EVEN domains of other subfa milies. Many sequence and chemical characteristics do not show systemic tre nds by subfamily or species of host organisms; such homoplasy is,widespread , Eighteen of the subfamilies are heterochimeric; in addition to multiple E F-hands they contain domains of other evolutionary origins.