Centrin isoforms in mammals. Relation to calmodulin.
In mammals, three calmodulin (CaM) genes code for 100% identical proteins. In these species, four centrin (Cetn) genes have been reported to exist. They are examined in this paper. While the gene for Cetn 1 contains no introns and appears to be derived from Cetn 2 by retroposition, a gene product for Cetn 1 is expressed. Cetn 2, 3, and 4 represent bona fide genes. The major difference between the members of the CaM and the Cetn subfamilies is the presence (usually) in Cetn of an approximately 23 amino acids long (but occasionally much longer) protruding amino acid end. In all members of these two subgroups, four EF hand motifs (in this paper taken as loops containing 12 amino acids) are separated by 24, 25 and 24 amino acids (each a helix-loop-helix) positioned between motifs 1and 2, 2 and 3, and 3 and 4, respectively. This rule applies not only to CaM and Cetn in mammals but also to these two subfamilies in simpler eukaryotes such as Saccharomyces cerevisiae and Giardia lamblia. The various mRNA products can be identified most readily by their characteristic 3' UTRs. While CaM is an ancient molecule that is expressed in all cells and is ubiquitous within these cells and interacts therein with almost 100 different proteins, many of which display the IQ or related binding motifs, the distribution and function of Cetn (an equally ancient molecule) is restricted mostly to basal bodies (e.g. in rods of the retina), axonemes, flagella, cilia and centrosomes. Are these two subclasses of calcium carriers (each molecule possessing four EF hands which possibly interact with different association constants)-if they are both present within a cell-randomly chosen for their service to the specific proteins with which they interact?
Friedberg
Felix
F
Department of Biochemistry and Molecular Biology, Howard University Medical School, Washington, DC, USA. ffriedberg@howard.edu
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000502:physiology; D002147:Calmodulin / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000502:physiology; D019143:Evolution, Molecular; D006801:Humans; D008322:Mammals / Q000235:genetics*; D008969:Molecular Sequence Data; D010802:Phylogeny; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D017385:Sequence Homology
D002135:Calcium-Binding Proteins; D002147:Calmodulin; D002868:Chromosomal Proteins, Non-Histone; D020033:Protein Isoforms; C056608:caltractin