Cloning of human calcineurin A: evidence for two isozymes and identification of a polyproline structural domain.
Two types (I and II) of cDNAs encoding the large (A) subunit of calcineurin, a calmodulin-regulated protein phosphatase, were isolated from human basal ganglia and brainstem mRNA. The complete sequences of the two calcineurin clones are identical except for a 54-base-pair insert in the type I clone and different 3' ends including part of the coding sequence for the C termini of the two proteins. These findings suggest that calcineurin A consists of at least two isozymes that may result from alternative splicing events. The two forms of the enzyme differ in the C terminus, which contains an inhibitory domain rapidly severed by limited proteolysis. With the exception of an 18-amino acid insert, the central parts of the molecules, which harbor the catalytic domains, are identical and show extended similarities with the entire catalytic subunits of protein phosphatases 1 and 2A, defining a distinct family of protein phosphatases. The 40-residue N-terminal fragment, specific for calcineurin, contains a sequence of 11 successive prolines that is also found in bovine brain calcineurin by peptide sequencing. A role in the calmodulin activation of calcineurin is proposed for this novel structural element.
Guerini
D
D
Laboratory of Biochemistry, National Cancer Institute, Bethesda, MD 20892.
Klee
C B
CB
D000595:Amino Acid Sequence; D000818:Animals; D001479:Basal Ganglia / Q000201:enzymology; D001483:Base Sequence; D015152:Blotting, Northern; D001933:Brain Stem / Q000201:enzymology; D019703:Calcineurin; D002148:Calmodulin-Binding Proteins / Q000235:genetics*; D002417:Cattle; D003001:Cloning, Molecular / Q000379:methods*; D015723:Gene Library; D005796:Genes; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000032:analysis; D010749:Phosphoprotein Phosphatases / Q000235:genetics*; D011487:Protein Conformation; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid
D002148:Calmodulin-Binding Proteins; D007527:Isoenzymes; D046911:Macromolecular Substances; D010455:Peptides; C011083:polyproline; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases