Abstract
Diacylglycerol kinase (DGK) family of proteins, which phosphorylates diacylglycerol into phosphatidic acid, play important role in controlling diverse cellular processes in eukaryotic organisms. Most vertebrate species contain 10 different DGK isozymes, which are grouped into 5 different classes based on the presence or absence of specific functional domains. However, the relationships among different DGK isozymes or how they have evolved from a common ancestor is unclear. The catalytic domain constitutes the single largest sequence element within the DGK proteins that is commonly and uniquely shared by all family members, but there is limited understanding of the overall function of this domain. In this work, we have used the catalytic domain sequences to construct a phylogenetic tree for the DGK family members from representatives of the main vertebrate classes and have also examined the distributions of various DGK isozymes in eukaryotic phyla. In a tree based on catalytic domain sequences, the DGK homologs belonging to different classes formed strongly supported clusters which were separated by long branches, and the different isozymes within each class also generally formed monophyletic groupings. Further, our analysis of the sequence alignments of catalytic domains has identified >10 novel sequence signatures consisting of conserved signature indels (inserts or deletions, CSIs) that are distinctive characteristics of either particular classes of DGK isozymes, or are commonly shared by members of two or more classes of DGK isozymes. The conserved indels in protein sequences are known to play important functional roles in the proteins/organisms where they are found. Thus, our identification of multiple highly specific CSIs that are distinguishing characteristics of different classes of DGK homologs points to the existence of important differences in the catalytic domain function among the DGK isozymes. The identified CSIs in conjunction with the results of blast searches on species distribution of DGK isozymes also provide useful insights into the evolutionary relationships among the DGK family of proteins.
Highlights
Diacylglycerol (DAG) and phosphatidic acid (PA) are two main signalling molecules within eukaryotic cells which, through their interactions with different effector proteins, play central roles in regulating diverse cellular processes [1,2,3,4,5,6]
Phylogenetic analysis of the DAG kinase (DGK) isozymes based on catalytic domain sequences The DGK isozymes differ considerably from each other in their sequence lengths and different domains present in them
Based on sequence alignments of DGK homologs from representatives of different groups of vertebrates, conserved regions from the catalytic domain which could be properly aligned amongst different DGK classes were identified and these were subjected to phylogenetic analyses
Summary
Diacylglycerol (DAG) and phosphatidic acid (PA) are two main signalling molecules within eukaryotic cells which, through their interactions with different effector proteins, play central roles in regulating diverse cellular processes [1,2,3,4,5,6]. Based on sequence similarities between these isozymes and the presence or absence of specific functional domains, the known DGK members have been grouped into 5 different classes or Types (Fig 1) [1,2,3,4,5,6,11,12] All of these isozymes share in common a large catalytic domain, which is sometimes divided into two parts–catalytic and accessory domains, and 2 or 3 cysteine-rich domains, referred to as the C1 domains [reviewed in[1,2,3,4,5,6,12, 13]]. The unique domains present in DGK isozymes, through their interactions with various regulatory proteins and other molecules present in different cells and tissues, play key roles in the diverse physiological functions exhibited by different DGK isozymes [1,2,3,4,5,6]
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