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Identification
HMDB Protein ID HMDBP10677
Secondary Accession Numbers
  • 16935
Name Neuropathy target esterase
Synonyms
  1. Patatin-like phospholipase domain-containing protein 6
Gene Name PNPLA6
Protein Type Enzyme
Biological Properties
General Function Involved in metabolic process
Specific Function Phospholipase B that deacylates intracellular phosphatidylcholine (PtdCho), generating glycerophosphocholine (GroPtdCho). This deacylation occurs at both sn-2 and sn-1 positions of PtdCho. Its specific chemical modification by certain organophosphorus (OP) compounds leads to distal axonopathy.
Pathways
  • Glycerophospholipid metabolism
Reactions
2-lysophosphatidylcholine + Water → Glycerophosphocholine + a carboxylate details
1-Acyl-sn-glycero-3-phosphocholine + Water → Glycerophosphocholine + Fatty acid details
2-Acyl-sn-glycero-3-phosphocholine + Water → Glycerophosphocholine + Fatty acid details
1-Acyl-sn-glycero-3-phosphoethanolamine + Water → Fatty acid + sn-glycero-3-Phosphoethanolamine details
2-Acyl-sn-glycero-3-phosphoethanolamine + Water → Fatty acid + sn-glycero-3-Phosphoethanolamine details
GO Classification
Biological Process
organ morphogenesis
lipid catabolic process
angiogenesis
phosphatidylcholine metabolic process
cell death
Cellular Component
endoplasmic reticulum membrane
integral to membrane
Component
membrane
cell part
endoplasmic reticulum membrane
organelle membrane
Function
hydrolase activity, acting on ester bonds
catalytic activity
hydrolase activity
lysophospholipase activity
carboxylesterase activity
Molecular Function
lysophospholipase activity
Process
metabolic process
primary metabolic process
phosphatidylcholine metabolic process
lipid metabolic process
organophosphate metabolic process
phospholipid metabolic process
glycerophospholipid metabolic process
Cellular Location
  1. Endoplasmic reticulum membrane
  2. Cytoplasmic side
  3. Single-pass type I membrane protein
Gene Properties
Chromosome Location 19
Locus 19p13.2
SNPs PNPLA6
Gene Sequence
>3984 bp
ATGGAGGCTCCGCTGCAAACTGGAATGGTGCTTGGCGTGATGATCGGGGCCGGAGTGGCG
GTGGTGGTCACGGCCGTGCTCATCCTCCTGGTGGTGCGGAGGCTGCGAGTGCCAAAAACC
CCAGCCCCGGATGGCCCCCGGTATCGGTTCCGGAAGAGGGACAAAGTGCTCTTCTATGGC
CGGAAGATTATGCGGAAGGTGTCACAATCCACCTCCTCCCTCGTGGATACCTCTGTCTCC
GCCACCTCCCGGCCACGCATGAGGAAGAAACTGAAGATGCTCAACATTGCCAAGAAGATC
CTGCGCATCCAGAAAGAGACGCCCACGCTGCAGCGGAAGGAGCCCCCGCCCGCAGTGCTA
GAAGCTGACCTGACCGAGGGCGACCTGGCTAACTCCCATCTGCCCTCTGAAGTGCTTTAT
ATGCTCAAGAACGTCCGGGTGCTGGGCCACTTCGAGAAGCCACTCTTCCTGGAGCTCTGC
CGCCACATGGTCTTCCAGCGGCTGGGCCAGGGTGACTACGTCTTCCGGCCGGGCCAGCCA
GATGCCAGCATCTACGTGGTGCAGGACGGGCTGCTGGAGCTCTGTCTGCCAGGGCCTGAC
GGGAAGGAGTGTGTGGTGAAGGAAGTGGTTCCTGGGGACAGCGTCAACAGCCTTCTCAGC
ATCCTGGATGTCATCACCGGTCACCAGCATCCCCAGCGGACCGTGTCTGCCCGGGCGGCC
CGGGACTCCACGGTGCTGCGCCTGCCGGTGGAAGCATTCTCCGCGGTCTTCACCAAGTAC
CCGGAGAGCTTGGTGCGGGTCGTGCAGATCATCATGGTGCGGCTGCAGCGAGTCACCTTC
CTGGCACTGCACAACTACCTGGGTCTGACCAATGAGCTCTTCAGCCACGAGATCCAGCCC
CTGCGTCTGTTCCCCAGCCCCGGCCTCCCAACTCGCACCAGCCCTGTGCGGGGCTCCAAG
AGAATGGTCAGCACCTCAGCTACAGACGAGCCCAGGGAGACCCCAGGGCGGCCACCCGAT
CCCACCGGGGCCCCGCTGCCTGGACCTACAGGGGACCCTGTGAAGCCCACATCCCTGGAA
ACCCCCTCGGCCCCTCTGCTGAGCCGCTGCGTCTCCATGCCAGGGGACATCTCAGGCTTG
CAGGGTGGCCCCCGCTCCGACTTCGACATGGCCTATGAGCGTGGCCGGATCTCCGTGTCC
CTGCAGGAAGAGGCCTCCGGGGGGTCCCTGGCAGCCCCCGCTCGGACCCCCACTCAGGAG
CCTCGTGAGCAGCCGGCAGGCGCCTGTGAATACAGCTACTGTGAGGATGAGTCGGCCACT
GGTGGCTGCCCTTTCGGGCCCTACCAGGGCCGCCAGACCAGCAGCATCTTCGAGGCAGCA
AAGCAGGAGCTGGCCAAGCTGATGCGGATTGAGGACCCCTCCCTCCTGAACAGCAGAGTC
TTGCTGCACCACGCCAAAGCTGGCACCATCATTGCCCGCCAGGGAGACCAGGACGTGAGC
CTGCACTTCGTGCTCTGGGGCTGCCTGCACGTGTACCAGCGCATGATCGACAAGGCGGAG
GACGTGTGCCTGTTCGTAGCGCAGCCCGGGGAACTGGTGGGGCAGCTGGCGGTGCTCACT
GGCGAACCTCTCATCTTCACACTGCGAGCCCAACGCGACTGCACCTTCCTGCGGATCTCC
AAGTCCGACTTCTATGAGATCATGCGCGCACAGCCCAGTGTGGTGCTGAGTGCGGCGCAC
ACGGTGGCAGCCAGGATGTCGCCCTTCGTGCGCCAGATGGACTTCGCCATCGACTGGACT
GCAGTGGAGGCGGGACGCGCGCTGTACAGGCAGGGCGACCGCTCCGACTGCACTTACATC
GTGCTCAATGGGCGGCTGCGTAGCGTGATCCAGCGAGGCAGTGGCAAGAAGGAGCTGGTG
GGCGAGTACGGCCGCGGCGACCTCATCGGCGTGGTGGAGGCACTGACCCGGCAGCCGCGA
GCCACGACGGTGCACGCGGTGCGCGACACGGAGCTGGCCAAGCTTCCCGAGGGCACCTTG
GGTCACATCAAACGCCGGTACCCGCAGGTCGTGACCCGCCTTATCCACCTACTGAGCCAG
AAAATTCTAGGGAATTTGCAGCAGCTGCAAGGACCCTTCCCAGCAGGCTCTGGGTTGGGT
GTGCCCCCACACTCGGAACTCACCAACCCAGCCAGCAACCTGGCAACTGTGGCAATCCTG
CCTGTGTGTGCTGAGGTCCCCATGGTGGCCTTCACGCTGGAGCTGCAGCACGCCCTGCAG
GCCATCGGTCCGACGCTACTCCTTAACAGTGACATCATCCGGGCACGCCTGGGGGCCTCC
GCACTGGATAGCATCCAAGAGTTCCGGCTGTCAGGGTGGCTGGCCCAGCAGGAGGATGCA
CACCGTATCGTACTCTACCAGACGGACGCCTCGCTGACGCCCTGGACCGTGCGCTGCCTG
CGACAGGCCGACTGCATCCTCATTGTGGGCCTGGGGGACCAGGAGCCTACCCTCGGCCAG
CTGGAGCAGATGCTGGAGAACACGGCTGTGCGCGCCCTTAAGCAGCTAGTCCTGCTCCAC
CGAGAGGAGGGCGCGGGCCCCACGCGCACCGTGGAGTGGCTAAATATGCGCAGCTGGTGC
TCGGGGCACCTGCACCTGCGCTGTCCGCGCCGCCTCTTTTCGCGCCGCAGCCCTGCCAAG
CTGCATGAGCTCTACGAGAAGGTTTTCTCCAGGCGCGCGGACCGGCACAGCGACTTCTCC
CGCTTGGCGAGGGTGCTCACGGGGAACACCATTGCCCTTGTGCTAGGCGGGGGCGGGGCC
AGGGGCTGCTCGCACATCGGAGTACTAAAGGCATTAGAGGAGGCGGGGGTCCCCGTGGAC
CTGGTGGGCGGCACGTCCATTGGCTCTTTCATCGGAGCGTTGTACGCGGAGGAGCGCAGC
GCCAGCCGCACGAAGCAGCGGGCCCGGGAGTGGGCCAAGAGCATGACTTCGGTGCTGGAA
CCTGTGTTGGACCTCACGTACCCAGTCACCTCCATGTTCACTGGGTCTGCCTTTAACCGC
AGCATCCATCGGGTCTTCCAGGATAAGCAGATTGAGGACCTGTGGCTGCCTTACTTCAAC
GTGACCACAGATATCACCGCCTCAGCCATGCGAGTCCACAAAGATGGCTCCCTGTGGCGG
TACGTGCGCGCCAGCATGACGCTGTCGGGCTACCTGCCCCCGCTGTGCGACCCCAAGGAC
GGGCACCTACTCATGGATGGCGGCTACATCAACAATCTGCCAGCGGACATCGCCCGCAGC
ATGGGTGCCAAAACGGTCATCGCCATTGACGTGGGGAGCCAGGATGAGACGGACCTCAGC
ACCTACGGGGACAGCCTGTCCGGCTGGTGGCTGCTGTGGAAGCGGCTGAATCCCTGGGCT
GACAAGGTAAAGGTTCCAGACATGGCTGAAATCCAGTCCCGCCTGGCCTACGTGTCCTGT
GTGCGGCAGCTAGAGGTTGTCAAGTCCAGCTCCTACTGCGAGTACCTGCGCCCGCCCATC
GACTGCTTCAAGACCATGGACTTTGGGAAGTTCGACCAGATCTATGATGTGGGCTACCAG
TACGGGAAGGCGGTGTTTGGAGGCTGGAGCCGTGGCAACGTCATTGAGAAAATGCTCACA
GACCGGCGGTCTACAGACCTTAATGAGAGCCGCCGTGCAGACGTGCTTGCCTTCCCAAGC
TCTGGCTTCACTGACTTGGCAGAGATTGTGTCCCGGATTGAGCCCCCCACGAGCTATGTC
TCTGATGGCTGTGCTGACGGAGAGGAGTCAGATTGTCTGACAGAGTATGAGGAGGACGCC
GGACCCGACTGCTCGAGGGATGAAGGGGGGTCCCCCGAGGGCGCAAGCCCCAGCACTGCC
TCCGAGATGGAGGAGGAGAAGTCGATTCTCCGGCAACGACGCTGTCTGCCCCAGGAGCCG
CCCGGCTCAGCCACAGATGCCTGA
Protein Properties
Number of Residues 1366
Molecular Weight 150952.43
Theoretical pI 7.734
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Neuropathy target esterase
MGTSSHGLATNSSGAKVAERDGFQDVLAPGEGSAGRICGAQPVPFVPQVLGVMIGAGVAV
VVTAVLILLVVRRLRVPKTPAPDGPRYRFRKRDKVLFYGRKIMRKVSQSTSSLVDTSVSA
TSRPRMRKKLKMLNIAKKILRIQKETPTLQRKEPPPAVLEADLTEGDLANSHLPSEVLYM
LKNVRVLGHFEKPLFLELCRHMVFQRLGQGDYVFRPGQPDASIYVVQDGLLELCLPGPDG
KECVVKEVVPGDSVNSLLSILDVITGHQHPQRTVSARAARDSTVLRLPVEAFSAVFTKYP
ESLVRVVQIIMVRLQRVTFLALHNYLGLTNELFSHEIQPLRLFPSPGLPTRTSPVRGSKR
MVSTSATDEPRETPGRPPDPTGAPLPGPTGDPVKPTSLETPSAPLLSRCVSMPGDISGLQ
GGPRSDFDMAYERGRISVSLQEEASGGSLAAPARTPTQEPREQPAGACEYSYCEDESATG
GCPFGPYQGRQTSSIFEAAKQELAKLMRIEDPSLLNSRVLLHHAKAGTIIARQGDQDVSL
HFVLWGCLHVYQRMIDKAEDVCLFVAQPGELVGQLAVLTGEPLIFTLRAQRDCTFLRISK
SDFYEIMRAQPSVVLSAAHTVAARMSPFVRQMDFAIDWTAVEAGRALYRQGDRSDCTYIV
LNGRLRSVIQRGSGKKELVGEYGRGDLIGVVEALTRQPRATTVHAVRDTELAKLPEGTLG
HIKRRYPQVVTRLIHLLSQKILGNLQQLQGPFPAGSGLGVPPHSELTNPASNLATVAILP
VCAEVPMVAFTLELQHALQAIGPTLLLNSDIIRARLGASALDSIQEFRLSGWLAQQEDAH
RIVLYQTDASLTPWTVRCLRQADCILIVGLGDQEPTLGQLEQMLENTAVRALKQLVLLHR
EEGAGPTRTVEWLNMRSWCSGHLHLRCPRRLFSRRSPAKLHELYEKVFSRRADRHSDFSR
LARVLTGNTIALVLGGGGARGCSHIGVLKALEEAGVPVDLVGGTSIGSFIGALYAEERSA
SRTKQRAREWAKSMTSVLEPVLDLTYPVTSMFTGSAFNRSIHRVFQDKQIEDLWLPYFNV
TTDITASAMRVHKDGSLWRYVRASMTLSGYLPPLCDPKDGHLLMDGGYINNLPADIARSM
GAKTVIAIDVGSQDETDLSTYGDSLSGWWLLWKRLNPWADKVKVPDMAEIQSRLAYVSCV
RQLEVVKSSSYCEYLRPPIDCFKTMDFGKFDQIYDVGYQYGKAVFGGWSRGNVIEKMLTD
RRSTDLNESRRADVLAFPSSGFTDLAEIVSRIEPPTSYVSDGCADGEESDCLTEYEEDAG
PDCSRDEGGSPEGASPSTASEMEEEKSILRQRRCLPQEPPGSATDA
GenBank ID Protein 116256487
UniProtKB/Swiss-Prot ID Q8IY17
UniProtKB/Swiss-Prot Entry Name PLPL6_HUMAN
PDB IDs Not Available
GenBank Gene ID Not Available
GeneCard ID PNPLA6
GenAtlas ID PNPLA6
HGNC ID HGNC:16268
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [PubMed:18669648 ]
  3. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. [PubMed:18691976 ]
  4. Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I: The full-ORF clone resource of the German cDNA Consortium. BMC Genomics. 2007 Oct 31;8:399. [PubMed:17974005 ]
  5. Grimwood J, Gordon LA, Olsen A, Terry A, Schmutz J, Lamerdin J, Hellsten U, Goodstein D, Couronne O, Tran-Gyamfi M, Aerts A, Altherr M, Ashworth L, Bajorek E, Black S, Branscomb E, Caenepeel S, Carrano A, Caoile C, Chan YM, Christensen M, Cleland CA, Copeland A, Dalin E, Dehal P, Denys M, Detter JC, Escobar J, Flowers D, Fotopulos D, Garcia C, Georgescu AM, Glavina T, Gomez M, Gonzales E, Groza M, Hammon N, Hawkins T, Haydu L, Ho I, Huang W, Israni S, Jett J, Kadner K, Kimball H, Kobayashi A, Larionov V, Leem SH, Lopez F, Lou Y, Lowry S, Malfatti S, Martinez D, McCready P, Medina C, Morgan J, Nelson K, Nolan M, Ovcharenko I, Pitluck S, Pollard M, Popkie AP, Predki P, Quan G, Ramirez L, Rash S, Retterer J, Rodriguez A, Rogers S, Salamov A, Salazar A, She X, Smith D, Slezak T, Solovyev V, Thayer N, Tice H, Tsai M, Ustaszewska A, Vo N, Wagner M, Wheeler J, Wu K, Xie G, Yang J, Dubchak I, Furey TS, DeJong P, Dickson M, Gordon D, Eichler EE, Pennacchio LA, Richardson P, Stubbs L, Rokhsar DS, Myers RM, Rubin EM, Lucas SM: The DNA sequence and biology of human chromosome 19. Nature. 2004 Apr 1;428(6982):529-35. [PubMed:15057824 ]
  6. Wang B, Malik R, Nigg EA, Korner R: Evaluation of the low-specificity protease elastase for large-scale phosphoproteome analysis. Anal Chem. 2008 Dec 15;80(24):9526-33. doi: 10.1021/ac801708p. [PubMed:19007248 ]
  7. Lush MJ, Li Y, Read DJ, Willis AC, Glynn P: Neuropathy target esterase and a homologous Drosophila neurodegeneration-associated mutant protein contain a novel domain conserved from bacteria to man. Biochem J. 1998 May 15;332 ( Pt 1):1-4. [PubMed:9576844 ]
  8. Lotti M: The pathogenesis of organophosphate polyneuropathy. Crit Rev Toxicol. 1991;21(6):465-87. [PubMed:1666291 ]
  9. Zaccheo O, Dinsdale D, Meacock PA, Glynn P: Neuropathy target esterase and its yeast homologue degrade phosphatidylcholine to glycerophosphocholine in living cells. J Biol Chem. 2004 Jun 4;279(23):24024-33. Epub 2004 Mar 25. [PubMed:15044461 ]
  10. Rainier S, Bui M, Mark E, Thomas D, Tokarz D, Ming L, Delaney C, Richardson RJ, Albers JW, Matsunami N, Stevens J, Coon H, Leppert M, Fink JK: Neuropathy target esterase gene mutations cause motor neuron disease. Am J Hum Genet. 2008 Mar;82(3):780-5. doi: 10.1016/j.ajhg.2007.12.018. Epub 2008 Feb 28. [PubMed:18313024 ]