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Abstract

Forty-five distinct subfamilies of EF-hand proteins have been identified. They contain from two to eight EF-hands that are recognizable by amino acid sequence as being statistically similar to other EF-hand domains. All proteins within one subfamily are congruent to one another, i.e. the dendrogram computed from one of the EF-hand domains is similar, within statistical error, to the dendrogram computed from another(s) domain. Thirteen subfamilies--including Calmodulin, Troponin C, Essential light chain, Regulatory light 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 gene duplications and speciations. The remaining 32 subfamilies do not show such general patterns of congruence; however, some--such as S100, intestinal calcium binding protein (calbindin 9 kd), and trichohylin--do not form congruent clusters of subfamilies. Nearly all of the domains 1, 3, 5, and 7 are most similar to other ODD domains. Correspondingly the EVEN numbered domains of all 45 subfamilies most closely resemble EVEN domains of other subfamilies. Many sequence and chemical characteristics do not show systemic trends by subfamily or species of host organisms; such homoplasy is widespread. Eighteen of the subfamilies are heterochimeric; in addition to multiple EF-hands they contain domains of other evolutionary origins.

Characterization and Implications of Ca2+Binding to Pectate Lyase C

“…The Ca 2ϩ binding motif found in PelC differs from the high affinity Ca 2ϩ sites found in EF-hand Ca 2ϩ -binding proteins (41)(42)(43)(44)(45). The typical EF-hand Ca 2ϩ binding site consists of a continuous or discontinuous helix-loop-helix motif on which the coordinating amino acids are located.…”

Neuronal Calcium Sensor-1 (Ncs1p) Is Up-regulated by Calcineurin to Promote Ca2+ Tolerance in Fission Yeast

“…Thus, stimulation of yeast cells by pheromones or other extracellular stimuli lead to an increase in intracellular Ca 2ϩ levels (10, 11) sensed by Ca 2ϩ -binding proteins belonging to the EF-hand superfamily (12). In S. pombe, a total of 23 genes specifies EF-hand-containing Ca 2ϩ -binding proteins, including cam1 (calmodulin) (13), cnb1 (calcineurin B) (14), and the recently characterized ncs1 gene (Ncs1p) (15), belonging to the neuronal calcium sensor (NCS) 2 family (16) expressed mostly in the central nervous system (17, 18).The primary sequence of S. pombe Ncs1p is Ͼ50% identical to neuronal homologs of the NCS branch of the EF-hand superfamily (19,20). Recoverin, the most intensively studied NCS protein, serves as a Ca 2ϩ sensor in retinal rod and cone cells where it controls the desensitization of rhodopsin (21-24).…”

“…The primary sequence of S. pombe Ncs1p is Ͼ50% identical to neuronal homologs of the NCS branch of the EF-hand superfamily (19,20). Recoverin, the most intensively studied NCS protein, serves as a Ca 2ϩ sensor in retinal rod and cone cells where it controls the desensitization of rhodopsin (21-24).…”

Genetic polymorphism and protein conformational plasticity in the calmodulin superfamily: Two ways to promote multifunctionality

“…Also, cell-specific expression of a unique set of components from the Ca 2ϩ signaling toolkit (3) is required for generating cell-specific responses to Ca 2ϩ signals. At the molecular level, a variety of Ca 2ϩ sensor proteins provide totally different physiological responses by stimulating or suppressing different intracellular signaling pathways (5)(6)(7).…”

“…In fact, this sequence is ranked fifth in an amino acid conservation contest in proteomes after the histones H4 and H3, actin B, and ubiquitin (61). In contrast, the troponin C family, which also contains four EF-hand motifs, has two isoforms in the human (skeletal and cardiac muscles) and many isoforms in invertebrates, all diverse in amino acid sequence (6). Similarly, the neuronal calcium sensor (NCS) and S100 proteins are diverse in sequence and function.…”