1-acyl-sn-glycerol-3-phosphate acyltransferase gamma (AGPAT3)
The protein contains 376 amino acids for an estimated molecular weight of 43381 Da.
Converts 1-acyl-sn-glycerol-3-phosphate (lysophosphatidic acid or LPA) into 1,2-diacyl-sn-glycerol-3-phosphate (phosphatidic acid or PA) by incorporating an acyl moiety at the sn-2 position of the glycerol backbone (PubMed:21173190). Acts on LPA containing saturated or unsaturated fatty acids C16:0-C20:4 at the sn-1 position using C18:1, C20:4 or C18:2-CoA as the acyl donor (PubMed:21173190). Also acts on lysophosphatidylcholine, lysophosphatidylinositol and lysophosphatidylserine using C18:1 or C20:4-CoA (PubMed:21173190). Has a preference for arachidonoyl-CoA as a donor (By similarity). Has also a modest lysophosphatidylinositol acyltransferase (LPIAT) activity, converts lysophosphatidylinositol (LPI) into phosphatidylinositol (By similarity). (updated: July 3, 2019)
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.
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, is predicted to be membranous by TOPCONS.
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Biological Process
CDP-diacylglycerol biosynthetic process
Cellular lipid metabolic process
Glycerophospholipid biosynthetic process
Phosphatidic acid biosynthetic process
Phospholipid biosynthetic process
Phospholipid metabolic process
Small molecule metabolic process
Triglyceride biosynthetic process
The reference OMIM entry for this protein is 614794
1-@acylglycerol-3-phosphate o-acyltransferase 3; agpat3
1-@acyl-sn-glycerol 3-phosphate acyltransferase 3
Lysophosphatidic acid acyltransferase, gamma
Lpaat-gamma
Lpaat3
DESCRIPTION
AGPAT3 is a member of a family of 1-acyl-sn-glycerol 3-phosphate acyltransferases (EC 2.3.1.51), also known as lysophosphatidic acid acyltransferases, that catalyze the acylation of lysophosphatidic acid to phosphatidic acid, the precursor of all glycerolipids (summary by Lu et al., 2005).CLONING
Lu et al. (2005) cloned mouse Agpat3. The deduced 376-amino acid protein has a putative N-terminal signal sequence and 3 transmembrane domains. It contains catalytic and substrate-binding motifs and a third motif conserved among AGPAT family members. RT-PCR analysis revealed variable but ubiquitous Agpat3 expression in mouse tissues. Schmidt et al. (2010) found that AGPAT3 contains 4 conserved motifs (I through IV) thought to be important for enzymatic activity, and a C-terminal trilysine (KKK) motif predicted to serve as an endoplasmic reticulum (ER) retention signal. They stated that AGPAT3 localized to both the ER and Golgi complex. Schmidt et al. (2010) also predicted that AGPAT3 contains only 2 transmembrane domains, 1 of which separates motifs I and II. Protease protection assays revealed that motif I was located in the cytoplasm and motif II localized to the ER and Golgi lumen. Using real-time PCR, Prasad et al. (2011) found that AGPAT3 was variably expressed in all human tissues examined, with highest expression in lung, spleen, and leukocytes. Fluorescence-tagged AGPAT3 localized to the ER and the nuclear envelope in transfected Chinese hamster ovary cells. Database analysis revealed orthologs of AGPAT3 in vertebrates, insects, and plants.GENE FUNCTION
Using RT-PCR, Lu et al. (2005) found that Ppar-alpha (170998) activation in mouse heart elevated Agpat3 expression. Schmidt et al. (2010) stated that they had determined that AGPAT3 is involved in regulating the structure and function of the Golgi complex and that AGPAT3 negatively regulates formation of Golgi membrane tubules. Mutagenesis experiments revealed that the C-terminal KKK motif of AGPAT3 was not required for localization to the ER and Golgi. Using a panel of lysophosphatidic acid (LPA) acceptor molecules and acyl-CoA donors, Prasad et al. (2011) found that AGPAT3 had a broad preference for LPA containing saturated or unsaturated long-chain fatty acids as acceptors, and preferentially utilized long-chain acyl-CoAs as acyl donors. This activity was similar to that of AGPAT5 (614796), but the 2 enzymes showed distinct acceptor and donor preferences. AGPAT3 also showed appreciable enzyme activity with lysophosphatidylcholine, lysophosphatidylinositol, and lysophosphatidylserine as acyl acceptor molecules when C18:1-CoA was the acyl donor.GENE STRUCTURE
Prasad et al. (2011) determined that the AGPAT3 gene contains 9 exons. The first exon is untranslated.MAPPING
Prasad et al. (2011) stated that the AGPAT3 gene maps to chromosome 21. Hartz (2012) mapped the AGPAT3 gene to chromosome 21q22.3 based on an alignment of the AGPAT3 sequence (GenBank GENBANK AF156774) with the genomic sequence (GRCh37). ... More on the omim web site
July 4, 2019: 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 15, 2016: Protein entry updated
Automatic update: OMIM entry 614794 was added.