Molecular properties of diacylglycerol kinase-epsilon in relation to function

Jennings, William; Doshi, Sejal; D’Souza, Kenneth; Epand, Richard M.

doi:10.1016/j.chemphyslip.2015.06.003

Cited by 9 publications

(23 citation statements)

References 48 publications

(86 reference statements)

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“…The DGK isozymes are primarily found in eukaryotic organisms. Although a protein exhibiting DGK activity is present in many bacteria [ 4 , 5 , 59 , 60 ], it shows minimal similarity (15–18%) over a short length, and with multiple intervening gaps, to the eukaryotic DGKs [ 13 ] [ 61 ]. The bacterial DGK homologs are short in comparison to the eukaryotic proteins and they do not contain any of the canonical sequence features (viz.…”

Section: Discussionmentioning

confidence: 99%

“…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 – 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 – 6 , 12 , 13 ]]. The simplest and shortest (567 aa) of these isozymes is DGK-ε, sole member of the class III DGK, which contains only the commonly shared catalytic domain and the two C1 domains.…”

Section: Introductionmentioning

confidence: 99%

“…The simplest and shortest (567 aa) of these isozymes is DGK-ε, sole member of the class III DGK, which contains only the commonly shared catalytic domain and the two C1 domains. In addition, DGK-ε also contains a conserved helical segment near its N-terminal end that is indicated to play an important role in its membrane interaction [ 12 , 13 ]. The class I DGKs (α, β and γ isozymes), in addition to containing the commonly shared domains, are characterized by the presence of two EF-hand motifs and a conserved domain of unknown function near the N-terminal end [ 1 – 6 , 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

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Phylogenetic analysis of the diacylglycerol kinase family of proteins and identification of multiple highly-specific conserved inserts and deletions within the catalytic domain that are distinctive characteristics of different classes of DGK homologs

Gupta

Epand

2017

PLoS ONE

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Phylogenetic analysis of the diacylglycerol kinase family of proteins and identification of multiple highly-specific conserved inserts and deletions within the catalytic domain that are distinctive characteristics of different classes of DGK homologs

Gupta

Epand

2017

PLoS ONE

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“…Escherichia coli is equipped with two forms of DGK (Van Horn and Sanders, 2012; Jennings et al, 2015) whereas mammalian cells contain at least 10 isozymes. In the course of evolution, one branch of the diversified DGKs might have gained substrate specificity toward arachidonate-containing DG.…”

Section: Discussionmentioning

confidence: 99%

Arachidonoyl-Specific Diacylglycerol Kinase ε and the Endoplasmic Reticulum

Nakano

Matsui

Tanaka

et al. 2016

Front. Cell Dev. Biol.

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The endoplasmic reticulum (ER) comprises an interconnected membrane network, which is made up of lipid bilayer and associated proteins. This organelle plays a central role in the protein synthesis and sorting. In addition, it represents the synthetic machinery of phospholipids, the major constituents of the biological membrane. In this process, phosphatidic acid (PA) serves as a precursor of all phospholipids, suggesting that PA synthetic activity is closely associated with the ER function. One enzyme responsible for PA synthesis is diacylglycerol kinase (DGK) that phosphorylates diacylglycerol (DG) to PA. DGK is composed of a family of enzymes with distinct features assigned to each isozyme in terms of structure, enzymology, and subcellular localization. Of DGKs, DGKε uniquely exhibits substrate specificity toward arachidonate-containing DG and is shown to reside in the ER. Arachidonic acid, a precursor of bioactive eicosanoids, is usually acylated at the sn-2 position of phospholipids, being especially enriched in phosphoinositide. In this review, we focus on arachidonoyl-specific DGKε with respect to the historical context, molecular basis of the substrate specificity and ER-targeting, and functional implications in the ER.

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“…23 Type III DGK (DGKe) has a unique substrate specificity for arachidonate-DAG. 24,25 This substrate specificity renders DGKe the most important isoform that catalyzes the first step of phosphatidylinositol (PI) resynthesis. Although there is no evidence supporting a direct role for DGKe in membrane trafficking, it is possible that of the DGK isoforms, only DGKe exerts an additional function mediating membrane trafficking via PtdIns cycling.…”

Section: Introductionmentioning

confidence: 99%