Neutral cholesterol ester hydrolase 1 (NCEH1)
The protein contains 408 amino acids for an estimated molecular weight of 45808 Da.
Hydrolyzes 2-acetyl monoalkylglycerol ether, the penultimate precursor of the pathway for de novo synthesis of platelet-activating factor (PubMed:17052608). May be responsible for cholesterol ester hydrolysis in macrophages (By similarity). Also involved in organ detoxification by hydrolyzing exogenous organophosphorus compounds (By similarity). May contribute to cancer pathogenesis by promoting tumor cell migration (PubMed:17052608). (updated: Aug. 12, 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.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- 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 annotated as membranous in UniProt.
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| Variant | Description |
|---|---|
| dbSNP:rs35316420 | |
| dbSNP:rs2302815 | |
| dbSNP:rs17857335 |
Biological Process
Catabolic process
Ether lipid metabolic process
Lipid catabolic process
Low-density lipoprotein particle clearance
Xenobiotic metabolic process
The reference OMIM entry for this protein is 613234
Neutral cholesterol ester hydrolase 1; nceh1
Nceh
Kiaa1363
CLONING
By sequencing clones obtained from a size-fractionated fetal brain cDNA library, Nagase et al. (2000) cloned NCEH1, which they designated KIAA1363. The deduced 430-amino acid protein shares significant similarity with rabbit hepatic esterase/N-deacetylase. RT-PCR ELISA detected highest NCEH1 expression in adult amygdala, followed by whole adult and fetal brain and most adult brain regions examined. Strong expression was also detected in adult kidney, heart, liver, skeletal muscle, and ovary and in fetal liver. Weaker expression was detected in all other adult tissues examined. Okazaki et al. (2008) cloned mouse Nceh. The deduced 408-amino acid protein contains an N-terminal transmembrane domain, a central catalytic core domain, and a C-terminal lipid-binding domain. Mouse and human HCEH share 87.5% amino acid identity. Northern blot analysis revealed high Nceh expression in mouse peritoneal macrophages and kidney, with weaker expression in heart and adrenal tissue, and none in other tissues examined. NCEH expression was low in freshly isolated human monocytes, but it was induced during differentiation to mature macrophages.GENE FUNCTION
Using integrated enzyme and small molecule profiling, Chiang et al. (2006) identified KIAA1363 as a 2-acetyl monoalkylglycerol ether hydrolase with a key regulatory role in an ether lipid signaling network. Pharmacologic inhibition of KIAA1363 in the SKOV-3 invasive ovarian cancer cell line dramatically reduced the levels of a specific set of lipophilic metabolites associated with aggressive cancers. Downregulation of KIAA1363 expression via short hairpin RNA resulted in a similar reduction in these metabolites, and it reduced the tumorigenicity of SKOV-3 cells following injection in immune-deficient mice. In vitro studies showed that the decreased tumorigenic potential of KIAA1363-knockdown SKOV-3 cells was due to reduced migration capacity rather than reduced cell proliferation. Unstable lipid-rich plaques in atherosclerosis are characterized by the accumulation of macrophage foam cells loaded with cholesterol ester (CE), which is reduced by CE hydrolases. Okazaki et al. (2008) found that membrane-bound Nceh accounted for a major part of the CE hydrolase activity in mouse peritoneal macrophages. Nceh showed a pH optimum of 7.2 with CE as substrate, and it also showed significant triacylglycerol hydrolase activity. RNA interference experiments showed that at least half of the CE hydrolase activity of mouse peritoneal macrophages was mediated by Nceh, and overexpression of Nceh was associated with decreased intracellular CE content. Immunohistochemical analysis revealed prominent expression of Nceh in macrophages surrounding atherosclerotic lesions in Apoe (107741) -/- mice. Nomura et al. (2010) found that KIAA1363 and MAGL (MGLL; 609699) were consistently elevated in aggressive human cancer cells relative to their nonaggressive counterparts. The authors suggested that enrichment of protumorigenic lipid signaling molecules in aggressive cancer cells supports their malignant phenotype.MAPPING
Hartz (2010) mapped the NCEH1 gene to chromosome 3q26.31 based on an alignment of the NCEH1 sequence (GenBank GENBANK AB037784) with the genomic sequence (GRCh37). ... More on the omim web site
Aug. 24, 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 613234 was added.