N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D (NAPEPLD)
The protein contains 393 amino acids for an estimated molecular weight of 45596 Da.
D-type phospholipase that hydrolyzes N-acyl-phosphatidylethanolamines (NAPEs) to produce bioactive N-acylethanolamines/fatty acid ethanolamides (NAEs/FAEs) and phosphatidic acid (PubMed:14634025, PubMed:16527816, PubMed:27571266, PubMed:25684574). Cleaves the terminal phosphodiester bond of diacyl- and alkenylacyl-NAPEs, primarily playing a role in the generation of long-chain saturated and monounsaturated NAEs in the brain (By similarity). May control NAPE homeostasis in dopaminergic neuron membranes and regulate neuron survival, partly through RAC1 activation (By similarity). As a regulator of lipid metabolism in the adipose tissue, mediates the crosstalk between adipocytes, gut microbiota and immune cells to control body temperature and weight. In particular, regulates energy homeostasis by promoting cold-induced brown or beige adipocyte differentiation program to generate heat from fatty acids and glucose. Has limited D-type phospholipase activity toward N-acyl lyso-NAPEs (By similarity). (updated: Oct. 7, 2020)
Protein identification was indicated in the following studies:
- 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.
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| Variant | Description |
|---|---|
| Almost no change in activity | |
| Almost no change in activity |
No binding partner found
Biological Process
Aging
Host-mediated regulation of intestinal microbiota composition
N-acylethanolamine metabolic process
N-acylphosphatidylethanolamine metabolic process
Negative regulation of eating behavior
Phospholipid catabolic process
Positive regulation of brown fat cell differentiation
Positive regulation of inflammatory response
Response to isolation stress
Retinoid metabolic process
Temperature homeostasis
The reference OMIM entry for this protein is 612334
N-acyl phosphatidylethanolamine-hydrolyzing phospholipase d; napepld
N-acyl phosphatidylethanolamine phospholipase d
DESCRIPTION
NAPEPLD is a phospholipase D type enzyme that catalyzes the release of N-acylethanolamine (NAE) from N-acyl-phosphatidylethanolamine (NAPE) in the second step of the biosynthesis of N-acylethanolamine (Okamoto et al., 2004).CLONING
By database analysis, followed by RT-PCR of a human megakaryoblastic leukemia cells, Okamoto et al. (2004) cloned NAPEPLD. The deduced 393-amino acid protein has a calculated molecular mass of 45.6 kD and shares 89.1% and 90.4% amino acid identity with its mouse and rat orthologs, respectively. Sequence analysis showed that NAPEPLD is a member of the zinc metallohydrolase family of the beta-lactamase fold. NAPEPLD contains a motif with highly conserved histidine and aspartic acid residues that plays a role in zinc coordination and hydrolysis reaction. NAPEPLD showed no homology with mammalian PLD1 (602382) and PLD2 (602384). Enzyme assay detected widespread distribution of activity in mouse tissues with highest activity in brain, kidney, and testis, and RT-PCR and Western blot assay showed a similar distribution pattern for NAPEPLD. Egertova et al. (2008) used in situ hybridization and immunohistochemistry to compare mRNA and protein levels in wildtype mouse brains and mice lacking Napepld. They showed that wildtype mice brains contain specific strong expression of Napepld mRNA and protein in the dentate gyrus granular cells. Immunoreactivity was localized to the granule cell axons (mossy fibers), as well as the axons of the vomeronasal nerve that projects to the accessory olfactory bulb, with weaker staining in the cerebellar cortex, thalamus, hypothalamus, and pyramidal cells in the hippocampus and neocortex. Egertova et al. (2008) suggested that NAPEPLD may generate N-acylethanolamines, such as anandamide, that act as neural signaling molecules regulating the activity of postsynaptic neurons.GENE FUNCTION
Okamoto et al. (2004) demonstrated that human, rat, and mouse recombinant NAPEPLD expressed in COS-7 cells exhibited enzyme activity to generate anandamide and other N-acylethanolamines from their corresponding N-acyl-phosphatidylethanolamines at comparable rates. NAPEPLD was inactive with phosphatidylcholine or phosphatidylethanolamine. Gillum et al. (2008) found that NAPEs were secreted into the circulation from the small intestine in rats in response to ingested fat. Systemic administration of the most abundant circulating NAPE at physiologic doses decreased food intake in rats.ANIMAL MODEL
Leung et al. (2006) showed that Napepld-null mice had greatly reduced brain levels of long-chain saturated NAEs but retained wildtype levels of polyunsaturated NAEs, such as anandamide. ... More on the omim web site
Oct. 20, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 612334 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).