PMID- 14644494 OWN - NLM STAT- MEDLINE DCOM- 20040217 LR - 20190708 IS - 0378-1119 (Print) IS - 0378-1119 (Linking) VI - 322 DP - 2003 Dec 11 TI - Organization and evolution of multifunctional Ca(2+)/CaM-dependent protein kinase genes. PG - 17-31 AB - The "multi-functional" Ca(2+) and calmodulin-dependent protein kinase, type II (CaMK-II) is an evolutionarily conserved protein. It has been found as a single gene in the horseshoe crab, marine sponge, sea urchin, nematode, and fruit fly, whereas most vertebrates possess four genes (alpha, beta, gamma, and delta). Species from fruit flies to humans encode alternative splice variants which are differentially targeted to phosphorylate diverse downstream targets of Ca(2+) signaling. By comparing known CaMK-II protein and nucleotide sequences, we have now provided evidence for the evolutionary relatedness of CaMK-IIs. Parsimony analyses unambiguously indicate that the four vertebrate CaMK-II genes arose via repeated duplications. Nucleotide phylogenies show consistent but moderate support for the placement of the vertebrate delta CaMK-II as the earliest diverging vertebrate gene. delta CaMK-II is the only gene with both central and C-terminal variable domains and has three to four times more intronic sequence than the other three genes. beta and gamma CaMK-II genes show strong sequence similarity and have comparable exon and intron organization and utilization. alpha CaMK-II is absent from amphibians (Xenopus laevis) and has the most restricted tissue specificity in mammals, whereas beta, gamma, and delta CaMK-IIs are expressed in most tissues. All 38 known mammalian CaMK-II splice variants were compiled with their tissue specificity and exon usage. Some of these variants use alternative 5' and 3' donors within a single exon as well as alternative promoters. These findings serve as an important benchmark for future phylogenetic, developmental, or biochemical studies on this important, conserved, and highly regulated gene family. FAU - Tombes, Robert M AU - Tombes RM AD - Department of Biology, Virginia Commonwealth University, Richmond, VA 23284-2012, USA. rmtombes@vcu.edu FAU - Faison, M Omar AU - Faison MO FAU - Turbeville, J M AU - Turbeville JM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Review PL - Netherlands TA - Gene JT - Gene JID - 7706761 RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases) SB - IM MH - Amino Acid Sequence MH - Animals MH - Calcium-Calmodulin-Dependent Protein Kinase Type 2 MH - Calcium-Calmodulin-Dependent Protein Kinases/*genetics/metabolism MH - *Evolution, Molecular MH - Gene Expression Regulation, Enzymologic MH - Genes/*genetics MH - Humans MH - Molecular Sequence Data MH - Phylogeny MH - Sequence Homology, Amino Acid RF - 114 EDAT- 2003/12/04 05:00 MHDA- 2004/02/18 05:00 CRDT- 2003/12/04 05:00 PHST- 2003/12/04 05:00 [pubmed] PHST- 2004/02/18 05:00 [medline] PHST- 2003/12/04 05:00 [entrez] AID - S0378111903008783 [pii] AID - 10.1016/j.gene.2003.08.023 [doi] PST - ppublish SO - Gene. 2003 Dec 11;322:17-31. doi: 10.1016/j.gene.2003.08.023.