Diacylglycerol kinase alpha (DGKA)
The protein contains 735 amino acids for an estimated molecular weight of 82630 Da.
Diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids (PubMed:2175712, PubMed:15544348). Thereby, acts as a central switch between the signaling pathways activated by these second messengers with different cellular targets and opposite effects in numerous biological processes (PubMed:2175712, PubMed:15544348). Also plays an important role in the biosynthesis of complex lipids (Probable). Can also phosphorylate 1-alkyl-2-acylglycerol in vitro as efficiently as diacylglycerol provided it contains an arachidonoyl group (PubMed:15544348). Also involved in the production of alkyl-lysophosphatidic acid, another bioactive lipid, through the phosphorylation of 1-alkyl-2-acetyl glycerol (PubMed:22627129). (updated: June 17, 2020)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology.
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| Variant | Description |
|---|---|
| dbSNP:rs17852990 |
No binding partner found
The reference OMIM entry for this protein is 125855
Diacylglycerol kinase, alpha, 80-kd; dgka
Diacylglycerol kinase, alpha; dagk1
Dagk, 80-kd
Dgk-alpha
DESCRIPTION
Diacylglycerol (DAG) kinases (DGKs or DAGKs; EC 2.7.1.107), such as DGKA, phosphorylate DAG to phosphatidic acid, thus removing DAG. Phosphatidic acid functions both in signaling and phospholipid synthesis. In intracellular signaling pathways, DAGK can be viewed as a modulator that competes with protein kinase C (PKC; see 600448) for the second messenger DAG (review by Topham and Prescott, 1999).CLONING
By sequencing tryptic peptides of DG kinase purified from human white blood cells, followed by PCR of human Jurkat leukemic T cells and screening human DND41 leukemic T cells, Schaap et al. (1990) obtained full-length DAGK cDNA. The deduced 735-amino acid protein has a calculated molecular mass of 82.7 kD. It has 2 EF-hand motifs predicted to bind calcium, 2 cysteine-repeat regions, 2 putative ATP-binding sites, and a C-terminal stretch of 110 amino acids that is fully conserved between human and pig DAGK. One of the ATP-binding sites is contained within the first cysteine-rich region. Northern blot analysis detected a 3.2-kb DAGK transcript in Jurkat cells and in normal human T cells. Purified human DAGK had an apparent molecular mass of 86 kD by SDS-PAGE and 87 kD by gel filtration.GENE FUNCTION
Schaap et al. (1990) found that DAGK purified from human white blood cells showed optimal activity in the presence of phosphatidylserine and deoxycholate. It showed relatively broad specificity, and DAG analogs containing an unsaturated fatty acid at the sn-2 position gave optimal enzymatic activity in the presence or absence of deoxycholate. Activity was not altered by calcium or calcium chelation. COS-7 cells overexpressing human DAGK showed 6- to 7-fold higher DAGK activity than controls. Several mammalian isozymes of DAGK have been identified. The isoform described by Schaap et al. (1990) has been designated DGK-alpha or DAGK1. Topham and Prescott (1999) stated that all DGKs have a conserved catalytic domain and at least 2 cysteine-rich regions homologous to the C1A and C1B motifs of PKCs. Most DGKs have structural motifs that are likely to play regulatory roles, and these motifs form the basis for dividing the DGKs into 5 subtypes. Type I DGKs, such as DGK-alpha, -beta (604070), and -gamma (601854), have calcium-binding EF-hand motifs at their N termini. DGK-delta (601826) and DKG-eta (604071) contain N-terminal pleckstrin homology (PH) domains and are defined as type II. DGK-epsilon (601440) contains no identifiable regulatory domains and is a type III DGK. The defining characteristic of type IV isozymes, such as DGK-zeta (601441) and -iota (604072), is that they have C-terminal ankyrin repeats. Group V is exemplified by DGK-theta (601207), which contains 3 cysteine-rich domains and a PH domain. Pilz et al. (1995) pointed to the growing evidence to support some form of light-activated phosphoinositide signal transduction pathway in the mammalian retina. Although this pathway had no obvious role in mammalian phototransduction, mutations in this pathway were known to cause retinal degeneration in Drosophila. For example, the 'retinal degeneration A' mutant in Drosophila is caused by an alteration in the eye-specific DAGK gene. To maintain cellular homeostasis, intracellular DAG levels must be tightly regulated. DAG functions in intracellular signaling pathways as an allosteric activator of PKC. In addition, DAG appears to play a role in regulating RAS (see 190020) and RHO (see 165370) family pr ... More on the omim web site
June 29, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 125855 was added.
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed