Neuropathy target esterase
| PNPLA6 | |||
|---|---|---|---|
| Identifiers | |||
Gene ontology | |||
| Molecular function | |||
| Cellular component | |||
| Biological process | |||
| Sources:Amigo / QuickGO | |||
| View/Edit Human | View/Edit Mouse |
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
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]
Function
Neuropathy target esterase is an enzyme with
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]
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.[8]
Recessively-inherited mutations in NTE that substantially reduce its catalytic activity cause a rare form of
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]
References
- ^ 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.
- ^ PMID 9576844.
- PMID 16799181.
- PMID 19029121.
- ^ a b c "Entrez Gene: PNPLA6 patatin-like phospholipase domain containing 6".
- PMID 16137924.
- PMID 16731034.
- PMID 12514188.
- PMID 15044461.
- S2CID 7075276.
- PMID 14749382.
- PMID 17015841.
- PMID 15772346.
- PMID 19759306.
- PMID 19675355.
- PMID 18313024.
- S2CID 1621142.
- S2CID 29313644.
- PMID 13192490.
- S2CID 4195141.
- PMID 4310054.
- PMID 8043002.
- PMID 20188121.
Further reading
- Glynn P (2000). "Neural development and neurodegeneration: two faces of neuropathy target esterase". Prog. Neurobiol. 61 (1): 61–74. S2CID 20322620.
- Maroni M, Bleecker ML (1986). "Neuropathy target esterase in human lymphocytes and platelets". Journal of Applied Toxicology. 6 (1): 1–7. S2CID 21763818.
- Bertoncin D, Russolo A, Caroldi S, Lotti M (1985). "Neuropathy target esterase in human lymphocytes". Arch. Environ. Health. 40 (3): 139–44. PMID 4026382.
- Gurba PE, Richardson RJ (1983). "Partial characterization of neurotoxic esterase of human placenta" (PDF). Toxicol. Lett. 15 (1): 13–7. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. S2CID 1235494.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.