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PNPLA6
Identifiers
Aliases	PNPLA6, BNHS, NTE, NTEMND, SPG39, iPLA2delta, sws, LNMS, OMCS, patatin like phospholipase domain containing 6
External IDs	OMIM: 603197; MGI: 1354723; HomoloGene: 21333; GeneCards: PNPLA6; OMA:PNPLA6 - orthologs
Gene location (Human) Chr. Chromosome 19 (human) Band 19p13.2 Start 7,534,004 bp End 7,561,764 bp
Gene location (Mouse) Chr. Chromosome 8 (mouse) Band 8 A1.1|8 1.92 cM Start 3,565,384 bp End 3,594,267 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in granulocyte upper lobe of left lung right frontal lobe anterior pituitary mucosa of transverse colon right lung right testis spleen left testis apex of heart Top expressed in neural layer of retina epithelium of small intestine superior frontal gyrus gastrula primary visual cortex vestibular membrane of cochlear duct right kidney lens epiblast duodenum More reference expression data BioGPS More reference expression data
Gene ontology Molecular function hydrolase activity lysophospholipase activity Cellular component integral component of membrane endoplasmic reticulum membrane endoplasmic reticulum membrane Biological process lipid catabolic process metabolism phosphatidylcholine metabolic process developmental process lipid metabolism glycerophospholipid catabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 10908 50767 Ensembl ENSG00000032444 ENSMUSG00000004565 UniProt Q8IY17 Q3TRM4 RefSeq (mRNA) NM_006702 NM_001166111 NM_001166112 NM_001166113 NM_001166114 NM_001122818 NM_015801 NM_001359121 NM_001359122 NM_001359123 NM_001359124 NM_001378951 NM_001378952 NM_001378953 NM_001378954 NM_001378955 RefSeq (protein) NP_001159583 NP_001159584 NP_001159585 NP_001159586 NP_006693 NP_001116290 NP_056616 NP_001346050 NP_001346051 NP_001346052 NP_001346053 NP_001365880 NP_001365881 NP_001365882 NP_001365883 NP_001365884 Location (UCSC) Chr 19: 7.53 – 7.56 Mb Chr 8: 3.57 – 3.59 Mb PubMed search
Wikidata
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Neuropathy target esterase, also known as patatin-like phospholipase domain-containing protein 6 (PNPLA6), is an esterase enzyme that in humans is encoded by the PNPLA6 gene.

Neuropathy target esterase is a phospholipase that deacetylates intracellular phosphatidylcholine to produce glycerophosphocholine. It is thought to function in neurite outgrowth and process elongation during neuronal differentiation. The protein is anchored to the cytoplasmic face of the endoplasmic reticulum in both neurons and non-neuronal cells.

Function

Neuropathy target esterase is an enzyme with phospholipase B activity: it sequentially hydrolyses both fatty acids from the major membrane lipid phosphatidylcholine, generating water-soluble glycerophosphocholine. In eukaryotic cells, NTE is anchored to the cytoplasmic face of the endoplasmic reticulum membrane. In mammals, it is particularly abundant in neurons, the placenta, and the kidney. Loss of NTE activity results in abnormally-elevated levels of phosphatidylcholine in the brain and impairment of the constitutive secretory pathway in neurons.

In the kidney, the expression of neuropathy target esterase is regulated by TonEBP as part of osmolyte production when the kidney produces concentrated urine.

Clinical significance

Mutations in this gene result in autosomal-recessive spastic paraplegia. The protein is also the target for neurodegeneration induced by organophosphorus compounds and chemical warfare agents.

Recessively-inherited mutations in NTE that substantially reduce its catalytic activity cause a rare form of hereditary spastic paraplegia (SPG39), in which distal parts of long spinal axons degenerate leading to limb weakness and paralysis. Organophosphate-induced delayed neuropathy— a paralysing syndrome with distal degeneration of long axons— results from poisoning with neuropathic organophosphorus compounds that irreversibly inhibit NTE.

References

1. ^ GRCh38: Ensembl release 89: ENSG00000032444 – Ensembl, May 2017
2. ^ GRCm38: Ensembl release 89: ENSMUSG00000004565 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. ^ Lush MJ, Li Y, Read DJ, Willis AC, Glynn P (Aug 1998). "Neuropathy target esterase and a homologous Drosophila neurodegeneration-associated mutant protein contain a novel domain conserved from bacteria to man". Biochem J. 332. ( Pt 1) (Pt 1): 1–4. doi:10.1042/bj3320001. PMC 1219444. PMID 9576844.
6. Wilson PA, Gardner SD, Lambie NM, Commans SA, Crowther DJ (Aug 2006). "Characterization of the human patatin-like phospholipase family". J Lipid Res. 47 (9): 1940–9. doi:10.1194/jlr.M600185-JLR200. PMID 16799181.
7. Kienesberger PC, Oberer M, Lass A, Zechner R (Apr 2009). "Mammalian patatin domain containing proteins: a family with diverse lipolytic activities involved in multiple biological functions". J Lipid Res. 50 Suppl (Supplement): S63–8. doi:10.1194/jlr.R800082-JLR200. PMC 2674697. PMID 19029121.
8. ^ "Entrez Gene: PNPLA6 patatin-like phospholipase domain containing 6".
9. Glynn P (September 2005). "Neuropathy target esterase and phospholipid deacylation". Biochim. Biophys. Acta. 1736 (2): 87–93. doi:10.1016/j.bbalip.2005.08.002. PMID 16137924.
10. Fernández-Murray JP, McMaster CR (March 2007). "Phosphatidylcholine synthesis and its catabolism by yeast neuropathy target esterase 1". Biochim. Biophys. Acta. 1771 (3): 331–6. doi:10.1016/j.bbalip.2006.04.004. PMID 16731034.
11. Li Y, Dinsdale D, Glynn P (March 2003). "Protein domains, catalytic activity, and subcellular distribution of neuropathy target esterase in Mammalian cells". J. Biol. Chem. 278 (10): 8820–5. doi:10.1074/jbc.M210743200. PMID 12514188.
12. Zaccheo O, Dinsdale D, Meacock PA, Glynn P (June 2004). "Neuropathy target esterase and its yeast homologue degrade phosphatidylcholine to glycerophosphocholine in living cells". J. Biol. Chem. 279 (23): 24024–33. doi:10.1074/jbc.M400830200. PMID 15044461.
13. Glynn P, Holton JL, Nolan CC, Read DJ, Brown L, Hubbard A, et al. (March 1998). "Neuropathy target esterase: immunolocalization to neuronal cell bodies and axons". Neuroscience. 83 (1): 295–302. doi:10.1016/S0306-4522(97)00388-6. PMID 9466418. S2CID 7075276.
14. Moser M, Li Y, Vaupel K, Kretzschmar D, Kluge R, Glynn P, et al. (February 2004). "Placental failure and impaired vasculogenesis result in embryonic lethality for neuropathy target esterase-deficient mice". Mol. Cell. Biol. 24 (4): 1667–79. doi:10.1128/mcb.24.4.1667-1679.2004. PMC 344166. PMID 14749382.
15. Gallazzini M, Ferraris JD, Kunin M, Morris RG, Burg MB (October 2006). "Neuropathy target esterase catalyzes osmoprotective renal synthesis of glycerophosphocholine in response to high NaCl". Proc. Natl. Acad. Sci. U.S.A. 103 (41): 15260–5. Bibcode:2006PNAS..10315260G. doi:10.1073/pnas.0607133103. PMC 1622810. PMID 17015841.
16. Mühlig-Versen M, da Cruz AB, Tschäpe JA, Moser M, Büttner R, Athenstaedt K, et al. (March 2005). "Loss of Swiss cheese/neuropathy target esterase activity causes disruption of phosphatidylcholine homeostasis and neuronal and glial death in adult Drosophila". J. Neurosci. 25 (11): 2865–73. doi:10.1523/JNEUROSCI.5097-04.2005. PMC 1182176. PMID 15772346.
17. Read DJ, Li Y, Chao MV, Cavanagh JB, Glynn P (September 2009). "Neuropathy target esterase is required for adult vertebrate axon maintenance". J. Neurosci. 29 (37): 11594–600. doi:10.1523/JNEUROSCI.3007-09.2009. PMC 3849655. PMID 19759306.
18. Gallazzini M, Burg MB (2009). "What's New About Osmotic Regulation of Glycerophosphocholine". Physiology. 24 (4): 245–249. doi:10.1152/physiol.00009.2009. PMC 2943332. PMID 19675355.
19. Rainier S, Bui M, Mark E, Thomas D, Tokarz D, Ming L, et al. (March 2008). "Neuropathy target esterase gene mutations cause motor neuron disease". Am. J. Hum. Genet. 82 (3): 780–5. doi:10.1016/j.ajhg.2007.12.018. PMC 2427280. PMID 18313024.
20. Rainier S, Albers JW, Dyck PJ, Eldevik OP, Wilcock S, Richardson RJ, et al. (January 2011). "Motor neuron disease due to neuropathy target esterase gene mutation: clinical features of the index families". Muscle Nerve. 43 (1): 19–25. doi:10.1002/mus.21777. hdl:2027.42/78477. PMID 21171093. S2CID 1621142.
21. Lotti M, Moretto A (2005). "Organophosphate-induced delayed polyneuropathy". Toxicol Rev. 24 (1): 37–49. doi:10.2165/00139709-200524010-00003. PMID 16042503. S2CID 29313644.
22. CAVANAGH JB (August 1954). "The toxic effects of triortho-cresyl phosphate on the nervous system; an experimental study in hens". J. Neurol. Neurosurg. Psychiatry. 17 (3): 163–72. doi:10.1136/jnnp.17.3.163. PMC 503178. PMID 13192490.
23. CASIDA JE, ETO M, BARON RL (September 1961). "Biological activity of a trio-cresyl phosphate metabolite". Nature. 191 (4796): 1396–7. Bibcode:1961Natur.191.1396C. doi:10.1038/1911396a0. PMID 13877086. S2CID 4195141.
24. Johnson MK (October 1969). "The delayed neurotoxic effect of some organophosphorus compounds. Identification of the phosphorylation site as an esterase". Biochem. J. 114 (4): 711–7. doi:10.1042/bj1140711. PMC 1184957. PMID 4310054.
25. Glynn P, Read DJ, Guo R, Wylie S, Johnson MK (July 1994). "Synthesis and characterization of a biotinylated organophosphorus ester for detection and affinity purification of a brain serine esterase: neuropathy target esterase". Biochem. J. 301 ( Pt 2) (2): 551–6. doi:10.1042/bj3010551. PMC 1137116. PMID 8043002.
26. Read DJ, Li Y, Chao MV, Cavanagh JB, Glynn P (May 2010). "Organophosphates induce distal axonal damage, but not brain oedema, by inactivating neuropathy target esterase". Toxicol. Appl. Pharmacol. 245 (1): 108–15. doi:10.1016/j.taap.2010.02.010. PMID 20188121.

Further reading

• Glynn P (2000). "Neural development and neurodegeneration: two faces of neuropathy target esterase". Prog. Neurobiol. 61 (1): 61–74. doi:10.1016/S0301-0082(99)00043-X. PMID 10759065. S2CID 20322620.
• Maroni M, Bleecker ML (1986). "Neuropathy target esterase in human lymphocytes and platelets". Journal of Applied Toxicology. 6 (1): 1–7. doi:10.1002/jat.2550060102. PMID 3958422. S2CID 21763818.
• Bertoncin D, Russolo A, Caroldi S, Lotti M (1985). "Neuropathy target esterase in human lymphocytes". Arch. Environ. Health. 40 (3): 139–44. doi:10.1080/00039896.1985.10545905. PMID 4026382.
• Gurba PE, Richardson RJ (1983). "Partial characterization of neurotoxic esterase of human placenta" (PDF). Toxicol. Lett. 15 (1): 13–7. doi:10.1016/0378-4274(83)90162-5. hdl:2027.42/25337. PMID 6836585.
• van Tienhoven M, Atkins J, Li Y, Glynn P (2002). "Human neuropathy target esterase catalyzes hydrolysis of membrane lipids". J. Biol. Chem. 277 (23): 20942–8. doi:10.1074/jbc.M200330200. PMID 11927584.
• Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Li Y, Dinsdale D, Glynn P (2003). "Protein domains, catalytic activity, and subcellular distribution of neuropathy target esterase in Mammalian cells". J. Biol. Chem. 278 (10): 8820–5. doi:10.1074/jbc.M210743200. PMID 12514188.
• Winrow CJ, Hemming ML, Allen DM, Quistad GB, Casida JE, Barlow C (2003). "Loss of neuropathy target esterase in mice links organophosphate exposure to hyperactivity". Nat. Genet. 33 (4): 477–85. doi:10.1038/ng1131. PMID 12640454.
• Zaccheo O, Dinsdale D, Meacock PA, Glynn P (2004). "Neuropathy target esterase and its yeast homologue degrade phosphatidylcholine to glycerophosphocholine in living cells". J. Biol. Chem. 279 (23): 24024–33. doi:10.1074/jbc.M400830200. PMID 15044461.
• Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, et al. (2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proc. Natl. Acad. Sci. U.S.A. 101 (33): 12130–5. Bibcode:2004PNAS..10112130B. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935.
• Chang PA, Wu YJ, Chen R, Li M, Li W, Qin QL (2005). "Inhibition of neuropathy target esterase expressing by antisense RNA does not affect neural differentiation in human neuroblastoma (SK-N-SH) cell line". Mol. Cell. Biochem. 272 (1–2): 47–54. doi:10.1007/s11010-005-6753-2. PMID 16010971. S2CID 20498617.
• Chang PA, Chen R, Wu YJ (2006). "Reduction of neuropathy target esterase does not affect neuronal differentiation, but moderate expression induces neuronal differentiation in human neuroblastoma (SK-N-SH) cell line". Brain Res. Mol. Brain Res. 141 (1): 30–8. doi:10.1016/j.molbrainres.2005.07.012. PMID 16122834. S2CID 22182434.
• Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, et al. (2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Res. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
• Chang PA, Liu ChY, Chen R, Wu YJ (2006). "Effect of over-expression of neuropathy target esterase on mammalian cell proliferation". Cell Prolif. 39 (5): 429–40. doi:10.1111/j.1365-2184.2006.00399.x. PMC 6496609. PMID 16987144.
• Chen R, Chang PA, Long DX, Yang L, Wu YJ (2007). "Down-regulation of neuropathy target esterase by protein kinase C activation with PMA stimulation". Mol. Cell. Biochem. 302 (1–2): 179–85. doi:10.1007/s11010-007-9439-0. PMID 17385009. S2CID 1235494.

• Biology

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

• Genes on human chromosome 19
• EC 3.1.1
• Enzymes