| IED ID | IndEnz0010000518 |
| Enzyme Type ID | esterase000518 |
| Protein Name |
Patatin-like phospholipase domain-containing protein 6 EC 3.1.1.5 Neuropathy target esterase |
| Gene Name | PNPLA6 NTE |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MEAPLQTGMMGTSSHGLATNSSGAKVAERDGFQDVLAPGEGSAGRICGAQPVPFVPQVLGVMIGAGVAVVVTAVLILLVVRRLRVPKTPAPDGPRYRFRKRDKVLFYGRKIMRKVSQSTSSLVDTSVSATSRPRMRKKLKMLNIAKKILRIQKETPTLQRKEPPPAVLEADLTEGDLANSHLPSEVLYMLKNVRVLGHFEKPLFLELCRHMVFQRLGQGDYVFRPGQPDASIYVVQDGLLELCLPGPDGKECVVKEVVPGDSVNSLLSILDVITGHQHPQRTVSARAARDSTVLRLPVEAFSAVFTKYPESLVRVVQIIMVRLQRVTFLALHNYLGLTNELFSHEIQPLRLFPSPGLPTRTSPVRGSKRMVSTSATDEPRETPGRPPDPTGAPLPGPTGDPVKPTSLETPSAPLLSRCVSMPGDISGLQGGPRSDFDMAYERGRISVSLQEEASGGSLAAPARTPTQEPREQPAGACEYSYCEDESATGGCPFGPYQGRQTSSIFEAAKQELAKLMRIEDPSLLNSRVLLHHAKAGTIIARQGDQDVSLHFVLWGCLHVYQRMIDKAEDVCLFVAQPGELVGQLAVLTGEPLIFTLRAQRDCTFLRISKSDFYEIMRAQPSVVLSAAHTVAARMSPFVRQMDFAIDWTAVEAGRALYRQGDRSDCTYIVLNGRLRSVIQRGSGKKELVGEYGRGDLIGVVEALTRQPRATTVHAVRDTELAKLPEGTLGHIKRRYPQVVTRLIHLLSQKILGNLQQLQGPFPAGSGLGVPPHSELTNPASNLATVAILPVCAEVPMVAFTLELQHALQAIGPTLLLNSDIIRARLGASALDSIQEFRLSGWLAQQEDAHRIVLYQTDASLTPWTVRCLRQADCILIVGLGDQEPTLGQLEQMLENTAVRALKQLVLLHREEGAGPTRTVEWLNMRSWCSGHLHLRCPRRLFSRRSPAKLHELYEKVFSRRADRHSDFSRLARVLTGNTIALVLGGGGARGCSHIGVLKALEEAGVPVDLVGGTSIGSFIGALYAEERSASRTKQRAREWAKSMTSVLEPVLDLTYPVTSMFTGSAFNRSIHRVFQDKQIEDLWLPYFNVTTDITASAMRVHKDGSLWRYVRASMTLSGYLPPLCDPKDGHLLMDGGYINNLPADIARSMGAKTVIAIDVGSQDETDLSTYGDSLSGWWLLWKRLNPWADKVKVPDMAEIQSRLAYVSCVRQLEVVKSSSYCEYLRPPIDCFKTMDFGKFDQIYDVGYQYGKAVFGGWSRGNVIEKMLTDRRSTDLNESRRADVLAFPSSGFTDLAEIVSRIEPPTSYVSDGCADGEESDCLTEYEEDAGPDCSRDEGGSPEGASPSTASEMEEEKSILRQRRCLPQEPPGSATDA |
| Enzyme Length | 1375 |
| Uniprot Accession Number | Q8IY17 |
| Absorption | |
| Active Site | ACT_SITE 1014; /note=Nucleophile; /evidence=ECO:0000255|PROSITE-ProRule:PRU01161; ACT_SITE 1134; /note=Proton acceptor; /evidence=ECO:0000255|PROSITE-ProRule:PRU01161 |
| Activity Regulation | ACTIVITY REGULATION: Inhibited by a series a OPs such as mipafox (MPX), phenyl saligenin phosphate (PSP), phenyl dipentyl phosphinate (PDPP), diisopropyl fluorophosphate and paraoxon. {ECO:0000269|PubMed:15044461, ECO:0000305|PubMed:1666291}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=a 1-acyl-sn-glycero-3-phosphocholine + H2O = a fatty acid + H(+) + sn-glycerol 3-phosphocholine; Xref=Rhea:RHEA:15177, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16870, ChEBI:CHEBI:28868, ChEBI:CHEBI:58168; EC=3.1.1.5; Evidence={ECO:0000269|PubMed:15044461};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15178; Evidence={ECO:0000269|PubMed:15044461}; CATALYTIC ACTIVITY: Reaction=1-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + H2O = (9Z)-octadecenoate + H(+) + sn-glycerol 3-phosphocholine; Xref=Rhea:RHEA:40807, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16870, ChEBI:CHEBI:28610, ChEBI:CHEBI:30823; Evidence={ECO:0000269|PubMed:11927584};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40808; Evidence={ECO:0000305|PubMed:11927584}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoylglycerol + H2O = glycerol + H(+) + hexadecanoate; Xref=Rhea:RHEA:39959, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:69081; Evidence={ECO:0000269|PubMed:11927584};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39960; Evidence={ECO:0000305|PubMed:11927584}; CATALYTIC ACTIVITY: Reaction=2-hexadecanoylglycerol + H2O = glycerol + H(+) + hexadecanoate; Xref=Rhea:RHEA:39963, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:75455; Evidence={ECO:0000269|PubMed:11927584};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39964; Evidence={ECO:0000305|PubMed:11927584}; CATALYTIC ACTIVITY: Reaction=1-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-octadecenoate + glycerol + H(+); Xref=Rhea:RHEA:38487, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:30823, ChEBI:CHEBI:75342; Evidence={ECO:0000269|PubMed:11927584};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38488; Evidence={ECO:0000305|PubMed:11927584}; CATALYTIC ACTIVITY: Reaction=2-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-octadecenoate + glycerol + H(+); Xref=Rhea:RHEA:38491, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:30823, ChEBI:CHEBI:73990; Evidence={ECO:0000269|PubMed:11927584};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38492; Evidence={ECO:0000305|PubMed:11927584}; CATALYTIC ACTIVITY: Reaction=2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + glycerol + H(+); Xref=Rhea:RHEA:26132, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:32395, ChEBI:CHEBI:52392; Evidence={ECO:0000269|PubMed:11927584};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:26133; Evidence={ECO:0000305|PubMed:11927584}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoyl-sn-glycero-3-phosphate + H2O = H(+) + hexadecanoate + sn-glycerol 3-phosphate; Xref=Rhea:RHEA:49092, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57518, ChEBI:CHEBI:57597; Evidence={ECO:0000250|UniProtKB:Q3TRM4};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49093; Evidence={ECO:0000250|UniProtKB:Q3TRM4}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoyl-sn-glycero-3-phosphocholine + H2O = H(+) + hexadecanoate + sn-glycerol 3-phosphocholine; Xref=Rhea:RHEA:40435, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16870, ChEBI:CHEBI:72998; Evidence={ECO:0000269|PubMed:11927584};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40436; Evidence={ECO:0000305|PubMed:11927584}; |
| DNA Binding | |
| EC Number | 3.1.1.5 |
| Enzyme Function | FUNCTION: Phospholipase B that deacylates intracellular phosphatidylcholine (PtdCho), generating glycerophosphocholine (GroPtdCho). This deacylation occurs at both sn-2 and sn-1 positions of PtdCho. Catalyzes the hydrolysis of several naturally occurring membrane-associated lipids (PubMed:11927584). Hydrolyzes lysophospholipids and monoacylglycerols, preferring the 1-acyl to the 2-acyl isomer. Does not catalyze hydrolysis of di- or triacylglycerols or fatty acid amides (PubMed:11927584). {ECO:0000269|PubMed:11927584, ECO:0000269|PubMed:15044461}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | NP_BIND 195..322; /note=cNMP 1; NP_BIND 511..633; /note=cNMP 2; NP_BIND 629..749; /note=cNMP 3 |
| Features | Active site (2); Alternative sequence (3); Chain (1); Compositional bias (2); Domain (1); Glycosylation (1); Modified residue (6); Motif (3); Natural variant (22); Nucleotide binding (3); Region (4); Sequence conflict (7); Topological domain (2); Transmembrane (1) |
| Keywords | Alternative splicing;Disease variant;Dwarfism;Endoplasmic reticulum;Glycoprotein;Hereditary spastic paraplegia;Hydrolase;Hypogonadotropic hypogonadism;Lipid degradation;Lipid metabolism;Membrane;Mental retardation;Neurodegeneration;Phosphoprotein;Reference proteome;Repeat;Retinitis pigmentosa;Transmembrane;Transmembrane helix |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000269|PubMed:15044461}; Single-pass type III membrane protein {ECO:0000269|PubMed:15044461}. |
| Modified Residue | MOD_RES 354; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"; MOD_RES 361; /note="Phosphothreonine"; /evidence="ECO:0007744|PubMed:18669648"; MOD_RES 362; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163"; MOD_RES 372; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 420; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"; MOD_RES 464; /note="Phosphothreonine"; /evidence="ECO:0007744|PubMed:24275569" |
| Post Translational Modification | PTM: Glycosylated. {ECO:0000269|PubMed:9576844}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 12514188; 16010971; 16122834; 16987144; 17015841; 17385009; 19059269; 19343046; 20306302; 20346913; 20380879; 20382209; 20603202; 21171093; 22903185; 23418070; 23902751; 25255935; 25267340; 25574898; 25631098; 26714052; 27317427; 27866050; 29749493; 30015775; 32623594; 33141049; 33184906; 33210227; 33650466; 33818269; |
| Motif | MOTIF 985..990; /note=GXGXXG; /evidence=ECO:0000255|PROSITE-ProRule:PRU01161; MOTIF 1012..1016; /note=GXSXG; /evidence=ECO:0000255|PROSITE-ProRule:PRU01161; MOTIF 1134..1136; /note=DGA/G; /evidence=ECO:0000255|PROSITE-ProRule:PRU01161 |
| Gene Encoded By | |
| Mass | 150,954 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=0.05 mM for 1-palmitoyl-lysophosphatidylcholine {ECO:0000269|PubMed:11927584}; KM=0.4 mM for 1-palmitoylglycerol {ECO:0000269|PubMed:11927584}; Vmax=20 umol/min/mg enzyme towards 1-palmitoyl-lysophosphatidylcholine {ECO:0000269|PubMed:11927584}; Vmax=1 umol/min/mg enzyme towards 1-palmitoylglycerol {ECO:0000269|PubMed:11927584}; |
| Metal Binding | |
| Rhea ID | RHEA:15177; RHEA:15178; RHEA:40807; RHEA:40808; RHEA:39959; RHEA:39960; RHEA:39963; RHEA:39964; RHEA:38487; RHEA:38488; RHEA:38491; RHEA:38492; RHEA:26132; RHEA:26133; RHEA:49092; RHEA:49093; RHEA:40435; RHEA:40436 |
| Cross Reference Brenda |