Neutral cholesterol ester hydrolase 1

Neutral cholesterol ester hydrolase 1 (NCEH) also known as arylacetamide deacetylase-like 1 (AADACL1) or KIAA1363 is an enzyme that in humans is encoded by the NCEH1 gene.^[5]

NCEH1
Identifiers
Aliases	NCEH1, AADACL1, NCEH, neutral cholesterol ester hydrolase 1
External IDs	OMIM: 613234; MGI: 2443191; HomoloGene: 23251; GeneCards: NCEH1; OMA:NCEH1 - orthologs
Gene location (Human) Chr. Chromosome 3 (human)[1] Band 3q26.31 Start 172,630,249 bp[1] End 172,711,218 bp[1]
Gene location (Mouse) Chr. Chromosome 3 (mouse)[2] Band 3|3 A3 Start 27,237,114 bp[2] End 27,338,757 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in lateral nuclear group of thalamus secondary oocyte islet of Langerhans prefrontal cortex Brodmann area 9 superior frontal gyrus right ventricle postcentral gyrus primary visual cortex caudate nucleus Top expressed in interventricular septum secondary oocyte primary oocyte otolith organ myocardium of ventricle utricle epithelium of stomach human kidney right kidney proximal tubule More reference expression data BioGPS n/a
Gene ontology Molecular function carboxylic ester hydrolase activity hydrolase activity sterol esterase activity serine hydrolase activity Cellular component integral component of membrane endoplasmic reticulum intracellular membrane-bounded organelle endoplasmic reticulum membrane membrane Biological process lipid catabolic process metabolism lipid metabolism catabolic process xenobiotic metabolic process low-density lipoprotein particle clearance Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 57552 320024 Ensembl ENSG00000144959 ENSMUSG00000027698 UniProt Q6PIU2 Q8BLF1 RefSeq (mRNA) NM_020792 NM_001146276 NM_001146277 NM_001146278 NM_178772 RefSeq (protein) NP_001139748 NP_001139749 NP_001139750 NP_065843 NP_848887 Location (UCSC) Chr 3: 172.63 – 172.71 Mb Chr 3: 27.24 – 27.34 Mb PubMed search [3] [4]
Wikidata
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NCEH is an enzyme located in the endoplasmic reticulum. NCEH hydrolyzes 2-acetyl monoalkylglycerol ether, as part of an enzymatic pathway regulating the levels of platelet activating factor and lysophospholipids that may be involved in cancer development.^[6][7]

Function

The enzymatic reaction catalyzed by NCEH is:^[6]

• 2-acetyl monoalkylglycerol ether → monoalkylglycerol ether

Monoalkylglycerol ethers (MAGEs) can then be converted to lysophospholipids alkyl-lysophosphatidic acid (alkyl-LPA) and alkyl-lysophosphatidylcholine (alkyl-LPC).

Controversial studies by one group also implicate the protein in the hydrolysis of cholesterol esters.^[8] However, loss of the protein in mice selectively reduces 2-acetyl monoalkylglycerol ether activity throughout the body.^[7]

Clinical significance

Evidence suggests a role for NCEH in cancer. Cancer cell lines contain unusually high levels of the protein.^[9] Reduction of the amount of NCEH1 in cancer cells reduces tumor migration and growth in mice and addition of alkyl-LPA restores these processes.^[6]

NCEH can break down organophosphates like the pesticide metabolite chlorpyrifos oxon.^[10] Conversely, enzymatic activity can be inhibited by organophosphates.^[11]

Structure

NCEH is a serine hydrolase that contains an N-terminal transmembrane domain, a central catalytic domain and a lipid-binding domain at its C-terminus.^[12] The protein exists in three isoforms that result from differences in mRNA splicing. Transcripts encode a protein for isoform a of 448, b of 440 and c of 275 amino acids long.

See also

• Autotaxin
• phosphatidic acid
• Lysophospholipid receptor
• LPA signaling