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Protein-coding gene in the species Homo sapiens
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 .
[5]
[6]
[7]
[8]
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.
[8]
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.
[9]
[10] 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.
[11]
[12]
[13]
[14]
[15] Loss of NTE activity results in abnormally-elevated levels of phosphatidylcholine in the brain and impairment of the
constitutive secretory pathway in neurons.
[5]
[16]
[17]
In the
kidney , the expression of neuropathy target esterase is regulated by
TonEBP as part of
osmolyte production when the kidney produces concentrated
urine .
[18]
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.
[8]
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.
[19]
[20]
Organophosphate-induced delayed neuropathy — a paralysing syndrome with distal degeneration of long axons— results from poisoning with neuropathic organophosphorus compounds that irreversibly inhibit NTE.
[21]
[22]
[23]
[24]
[25]
[26]
^
a
b
c
GRCh38: Ensembl release 89: ENSG00000032444 –
Ensembl , May 2017
^
a
b
c
GRCm38: Ensembl release 89: ENSMUSG00000004565 –
Ensembl , May 2017
^
"Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^
"Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^
a
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^ Kienesberger PC, Oberer M, Lass A, Zechner R (Apr 2009).
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^
a
b
c
"Entrez Gene: PNPLA6 patatin-like phospholipase domain containing 6" .
^ Glynn P (September 2005). "Neuropathy target esterase and phospholipid deacylation". Biochim. Biophys. Acta . 1736 (2): 87–93.
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^ 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.
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^ 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.
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PMID
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^ 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.
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PMID
15044461 .
^ 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 :
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PMID
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S2CID
7075276 .
^ 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.
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^ Gallazzini M, Ferraris JD, Kunin M, Morris RG, Burg MB (October 2006).
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2006PNAS..10315260G .
doi :
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PMC
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PMID
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^ 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.
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PMC
1182176 .
PMID
15772346 .
^ 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 :
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PMC
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PMID
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^ Gallazzini M, Burg MB (2009).
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PMC
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PMID
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^ Rainier S, Bui M, Mark E, Thomas D, Tokarz D, Ming L, et al. (March 2008).
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PMC
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PMID
18313024 .
^ 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.
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PMID
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S2CID
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PMID
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29313644 .
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PMID
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4195141 .
^ Johnson MK (October 1969).
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^ Glynn P, Read DJ, Guo R, Wylie S, Johnson MK (July 1994).
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^ 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.
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PMID
10759065 .
S2CID
20322620 .
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21763818 .
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"Protein domains, catalytic activity, and subcellular distribution of neuropathy target esterase in Mammalian cells" . J. Biol. Chem . 278 (10): 8820–5.
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10.1074/jbc.M210743200 .
PMID
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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 .
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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.
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22182434 .
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S2CID
1235494 .
Activity Regulation Classification Kinetics Types
This article incorporates text from the
United States National Library of Medicine , which is in the
public domain .