NAPEP_HUMAN
ID NAPEP_HUMAN Reviewed; 393 AA.
AC Q6IQ20; Q5CZ87; Q769K1;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-FEB-2008, sequence version 2.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D {ECO:0000303|PubMed:25684574};
DE Short=N-acyl phosphatidylethanolamine phospholipase D;
DE Short=NAPE-PLD {ECO:0000303|PubMed:25684574};
DE Short=NAPE-hydrolyzing phospholipase D;
DE EC=3.1.4.54 {ECO:0000269|PubMed:14634025, ECO:0000269|PubMed:16527816, ECO:0000269|PubMed:25684574};
GN Name=NAPEPLD; Synonyms=C7orf18;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=14634025; DOI=10.1074/jbc.m306642200;
RA Okamoto Y., Morishita J., Tsuboi K., Tonai T., Ueda N.;
RT "Molecular characterization of a phospholipase D generating anandamide and
RT its congeners.";
RL J. Biol. Chem. 279:5298-5305(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=15820312; DOI=10.1016/j.ygeno.2005.01.013;
RA Curtiss N.P., Bonifas J.M., Lauchle J.O., Balkman J.D., Kratz C.P.,
RA Emerling B.M., Green E.D., Le Beau M.M., Shannon K.M.;
RT "Isolation and analysis of candidate myeloid tumor suppressor genes from a
RT commonly deleted segment of 7q22.";
RL Genomics 85:600-607(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ASN-389.
RC TISSUE=Colon carcinoma;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ASN-389.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ASN-389.
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, MUTAGENESIS OF LEU-207
RP AND HIS-380, AND VARIANTS ALA-152 AND ASN-389.
RX PubMed=16527816; DOI=10.1074/jbc.m512359200;
RA Wang J., Okamoto Y., Morishita J., Tsuboi K., Miyatake A., Ueda N.;
RT "Functional analysis of the purified anandamide-generating phospholipase D
RT as a member of the metallo-beta-lactamase family.";
RL J. Biol. Chem. 281:12325-12335(2006).
RN [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY
RP REGULATION.
RX PubMed=27571266; DOI=10.1021/acschembio.6b00624;
RA Margheritis E., Castellani B., Magotti P., Peruzzi S., Romeo E., Natali F.,
RA Mostarda S., Gioiello A., Piomelli D., Garau G.;
RT "Bile Acid Recognition by NAPE-PLD.";
RL ACS Chem. Biol. 11:2908-2914(2016).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) IN COMPLEX WITH ZINC AND DEOXYCHOLIC
RP ACID, CATALYTIC ACTIVITY, ACTIVITY REGULATION, FUNCTION, MUTAGENESIS OF
RP GLN-158; TYR-159 AND ARG-257, COFACTOR, SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=25684574; DOI=10.1016/j.str.2014.12.018;
RA Magotti P., Bauer I., Igarashi M., Babagoli M., Marotta R., Piomelli D.,
RA Garau G.;
RT "Structure of human N-acylphosphatidylethanolamine-hydrolyzing
RT phospholipase D: regulation of fatty acid ethanolamide biosynthesis by bile
RT acids.";
RL Structure 23:598-604(2015).
CC -!- FUNCTION: D-type phospholipase that hydrolyzes N-acyl-
CC phosphatidylethanolamines (NAPEs) to produce bioactive N-
CC acylethanolamines/fatty acid ethanolamides (NAEs/FAEs) and phosphatidic
CC acid (PubMed:14634025, PubMed:16527816, PubMed:27571266,
CC PubMed:25684574). Cleaves the terminal phosphodiester bond of
CC diacyl- and alkenylacyl-NAPEs, primarily playing a role in the
CC generation of long-chain saturated and monounsaturated NAEs in the
CC brain (By similarity). May control NAPE homeostasis in dopaminergic
CC neuron membranes and regulate neuron survival, partly through RAC1
CC activation (By similarity). As a regulator of lipid metabolism in the
CC adipose tissue, mediates the crosstalk between adipocytes, gut
CC microbiota and immune cells to control body temperature and weight. In
CC particular, regulates energy homeostasis by promoting cold-induced
CC brown or beige adipocyte differentiation program to generate heat from
CC fatty acids and glucose. Has limited D-type phospholipase activity
CC toward N-acyl lyso-NAPEs (By similarity).
CC {ECO:0000250|UniProtKB:Q8BH82, ECO:0000269|PubMed:14634025,
CC ECO:0000269|PubMed:16527816, ECO:0000269|PubMed:25684574,
CC ECO:0000269|PubMed:27571266}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-acyl-1,2-diacyl-sn-glycero-3-phosphoethanolamine = a
CC 1,2-diacyl-sn-glycero-3-phosphate + an N-acylethanolamine + H(+);
CC Xref=Rhea:RHEA:33159, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:52640, ChEBI:CHEBI:58608, ChEBI:CHEBI:62537; EC=3.1.4.54;
CC Evidence={ECO:0000269|PubMed:14634025, ECO:0000269|PubMed:16527816,
CC ECO:0000269|PubMed:25684574, ECO:0000269|PubMed:27571266};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33160;
CC Evidence={ECO:0000305|PubMed:14634025, ECO:0000305|PubMed:16527816,
CC ECO:0000305|PubMed:25684574, ECO:0000305|PubMed:27571266};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-butanoyl-1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-
CC glycero-3-phosphoethanolamine = 1-hexadecanoyl-2-(9Z,12Z-
CC octadecadienoyl)-sn-glycero-3-phosphate + H(+) + N-butanoyl
CC ethanolamine; Xref=Rhea:RHEA:45620, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:72860, ChEBI:CHEBI:85298,
CC ChEBI:CHEBI:85304; Evidence={ECO:0000250|UniProtKB:Q769K2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45621;
CC Evidence={ECO:0000250|UniProtKB:Q769K2};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-hexanoyl-1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-
CC glycero-3-phosphoethanolamine = 1-hexadecanoyl-2-(9Z,12Z-
CC octadecadienoyl)-sn-glycero-3-phosphate + H(+) + N-hexanoyl
CC ethanolamine; Xref=Rhea:RHEA:45616, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:72860, ChEBI:CHEBI:85297,
CC ChEBI:CHEBI:85303; Evidence={ECO:0000250|UniProtKB:Q769K2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45617;
CC Evidence={ECO:0000250|UniProtKB:Q769K2};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-octanoyl-1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-
CC glycero-3-phosphoethanolamine = 1-hexadecanoyl-2-(9Z,12Z-
CC octadecadienoyl)-sn-glycero-3-phosphate + H(+) + N-octanoyl
CC ethanolamine; Xref=Rhea:RHEA:45612, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:72860, ChEBI:CHEBI:85296,
CC ChEBI:CHEBI:85302; Evidence={ECO:0000250|UniProtKB:Q769K2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45613;
CC Evidence={ECO:0000250|UniProtKB:Q769K2};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-decanoyl-1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-
CC glycero-3-phosphoethanolamine = 1-hexadecanoyl-2-(9Z,12Z-
CC octadecadienoyl)-sn-glycero-3-phosphate + H(+) + N-decanoyl
CC ethanolamine; Xref=Rhea:RHEA:45608, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:72860, ChEBI:CHEBI:85295,
CC ChEBI:CHEBI:85301; Evidence={ECO:0000250|UniProtKB:Q769K2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45609;
CC Evidence={ECO:0000250|UniProtKB:Q769K2};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-dodecanoyl-1,2-di-(9Z-octadecenoyl)-sn-glycero-3-
CC phosphoethanolamine = 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphate
CC + H(+) + N-dodecanoylethanolamine; Xref=Rhea:RHEA:45556,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:74546,
CC ChEBI:CHEBI:85263, ChEBI:CHEBI:85294;
CC Evidence={ECO:0000250|UniProtKB:Q769K2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45557;
CC Evidence={ECO:0000250|UniProtKB:Q769K2};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-tetradecanoyl-1,2-di-(9Z-octadecenoyl)-sn-glycero-3-
CC phosphoethanolamine = 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphate
CC + H(+) + N-tetradecanoylethanolamine; Xref=Rhea:RHEA:45552,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:74546,
CC ChEBI:CHEBI:85262, ChEBI:CHEBI:85293;
CC Evidence={ECO:0000250|UniProtKB:Q769K2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45553;
CC Evidence={ECO:0000250|UniProtKB:Q769K2};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-hexadecanoyl-1,2-di-(9Z-octadecenoyl)-sn-glycero-3-
CC phosphoethanolamine = 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphate
CC + H(+) + N-hexadecanoylethanolamine; Xref=Rhea:RHEA:45540,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:71464,
CC ChEBI:CHEBI:74546, ChEBI:CHEBI:78097;
CC Evidence={ECO:0000269|PubMed:16527816};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45541;
CC Evidence={ECO:0000305|PubMed:16527816};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N,1-dihexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-
CC glycero-3-phosphoethanolamine = 1-hexadecanoyl-2-(9Z,12Z-
CC octadecadienoyl)-sn-glycero-3-phosphate + H(+) + N-
CC hexadecanoylethanolamine; Xref=Rhea:RHEA:45596, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:71464, ChEBI:CHEBI:72860,
CC ChEBI:CHEBI:85334; Evidence={ECO:0000250|UniProtKB:Q8BH82};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45597;
CC Evidence={ECO:0000250|UniProtKB:Q8BH82};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-octadecanoyl-1,2-di-(9Z-octadecenoyl)-sn-glycero-3-
CC phosphoethanolamine = 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphate
CC + H(+) + N-octadecanoyl ethanolamine; Xref=Rhea:RHEA:45536,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:74546,
CC ChEBI:CHEBI:85292, ChEBI:CHEBI:85299;
CC Evidence={ECO:0000250|UniProtKB:Q769K2,
CC ECO:0000250|UniProtKB:Q8BH82};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45537;
CC Evidence={ECO:0000250|UniProtKB:Q769K2,
CC ECO:0000250|UniProtKB:Q8BH82};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N,1,2-tri-(9Z-octadecenoyl)-sn-glycero-3-
CC phosphoethanolamine = 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphate
CC + H(+) + N-(9Z-octadecenoyl) ethanolamine; Xref=Rhea:RHEA:45532,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:71466,
CC ChEBI:CHEBI:74546, ChEBI:CHEBI:85291;
CC Evidence={ECO:0000250|UniProtKB:Q769K2,
CC ECO:0000250|UniProtKB:Q8BH82};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45533;
CC Evidence={ECO:0000250|UniProtKB:Q769K2,
CC ECO:0000250|UniProtKB:Q8BH82};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-1,2-diacyl-sn-
CC glycero-3-phosphoethanolamine = a 1,2-diacyl-sn-glycero-3-phosphate +
CC H(+) + N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine;
CC Xref=Rhea:RHEA:56548, ChEBI:CHEBI:2700, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:58608, ChEBI:CHEBI:140532;
CC Evidence={ECO:0000269|PubMed:27571266};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:56549;
CC Evidence={ECO:0000305|PubMed:27571266};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-1,2-di-(9Z-
CC octadecenoyl)-sn-glycero-3-phosphoethanolamine = 1,2-di-(9Z-
CC octadecenoyl)-sn-glycero-3-phosphate + H(+) + N-(5Z,8Z,11Z,14Z-
CC eicosatetraenoyl)-ethanolamine; Xref=Rhea:RHEA:45528,
CC ChEBI:CHEBI:2700, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:74546, ChEBI:CHEBI:85277;
CC Evidence={ECO:0000250|UniProtKB:Q769K2,
CC ECO:0000250|UniProtKB:Q8BH82};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45529;
CC Evidence={ECO:0000250|UniProtKB:Q769K2,
CC ECO:0000250|UniProtKB:Q8BH82};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(1Z-octadecenoyl)-2-(9Z-octadecenoyl)-sn-glycero-3-phospho-
CC N-hexadecanoyl-ethanolamine + H2O = 1-O-(1Z-octadecenoyl)-2-(9Z-
CC octadecenoyl)-sn-glycero-3-phosphate + H(+) + N-
CC hexadecanoylethanolamine; Xref=Rhea:RHEA:56464, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:71464, ChEBI:CHEBI:138663,
CC ChEBI:CHEBI:140452; Evidence={ECO:0000250|UniProtKB:Q8BH82};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:56465;
CC Evidence={ECO:0000250|UniProtKB:Q8BH82};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N,1-diacyl-sn-glycero-3-phosphoethanolamine = a 1-acyl-
CC sn-glycero-3-phosphate + an N-acylethanolamine + H(+);
CC Xref=Rhea:RHEA:53164, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:52640, ChEBI:CHEBI:57970, ChEBI:CHEBI:85216;
CC Evidence={ECO:0000250|UniProtKB:Q8BH82};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53165;
CC Evidence={ECO:0000250|UniProtKB:Q8BH82};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N,1-dihexadecanoyl-sn-glycero-3-phosphoethanolamine = 1-
CC hexadecanoyl-sn-glycero-3-phosphate + H(+) + N-
CC hexadecanoylethanolamine; Xref=Rhea:RHEA:45592, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57518, ChEBI:CHEBI:71464,
CC ChEBI:CHEBI:85335; Evidence={ECO:0000250|UniProtKB:Q8BH82};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45593;
CC Evidence={ECO:0000250|UniProtKB:Q8BH82};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-1-(9Z-octadecenoyl)-
CC sn-glycero-3-phosphoethanolamine = 1-(9Z-octadecenoyl)-sn-glycero-3-
CC phosphate + H(+) + N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine;
CC Xref=Rhea:RHEA:45544, ChEBI:CHEBI:2700, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:74544, ChEBI:CHEBI:85223;
CC Evidence={ECO:0000250|UniProtKB:Q8BH82};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45545;
CC Evidence={ECO:0000250|UniProtKB:Q8BH82};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000305|PubMed:25684574};
CC Note=Binds 2 zinc divalent cations per subunit.
CC {ECO:0000269|PubMed:25684574};
CC -!- ACTIVITY REGULATION: Activated by divalent cations (PubMed:16527816).
CC Activated by bile acids and their conjugates, except for lithocholic
CC acid which is rather inhibitory. Binding of deoxycholic acid favors the
CC selective release of anandamide and likely other unsatured long FAEs
CC (PubMed:27571266, PubMed:25684574). Inhibited by
CC phosphatidylethanolamines (PubMed:25684574).
CC {ECO:0000269|PubMed:16527816, ECO:0000269|PubMed:25684574,
CC ECO:0000269|PubMed:27571266}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=9 uM for N-hexadecanoyl-1,2-diacyl-sn-glycero-3-
CC phosphoethanolamine (in the presence of deoxycholic acid)
CC {ECO:0000269|PubMed:27571266};
CC KM=9 uM for N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-1,2-diacyl-sn-glycero-
CC 3-phosphoethanolamine (in the presence of deoxycholic acid)
CC {ECO:0000269|PubMed:27571266};
CC Vmax=156 nmol/min/mg enzyme toward N-hexadecanoyl-1,2-diacyl-sn-
CC glycero-3-phosphoethanolamine (in the presence of deoxycholic acid)
CC {ECO:0000269|PubMed:27571266};
CC Vmax=1131 nmol/min/mg enzyme toward N-(5Z,8Z,11Z,14Z-
CC eicosatetraenoyl)-1,2-diacyl-sn-glycero-3-phosphoethanolamine (in the
CC presence of deoxycholic acid) {ECO:0000269|PubMed:27571266};
CC -!- SUBUNIT: Homodimer. Bile acids promote the assembly of inactive
CC monomers into an active dimer and enable catalysis.
CC {ECO:0000269|PubMed:25684574}.
CC -!- INTERACTION:
CC Q6IQ20; Q6IQ20: NAPEPLD; NbExp=3; IntAct=EBI-16143143, EBI-16143143;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000269|PubMed:25684574}; Peripheral membrane protein
CC {ECO:0000305|PubMed:25684574}. Early endosome membrane
CC {ECO:0000269|PubMed:25684574}; Peripheral membrane protein
CC {ECO:0000305|PubMed:25684574}. Nucleus envelope
CC {ECO:0000269|PubMed:25684574}. Nucleus, nucleoplasm
CC {ECO:0000269|PubMed:25684574}. Note=Localized in the proximity of the
CC cellular membranes likely through interaction with membrane
CC phospholipids. {ECO:0000269|PubMed:25684574}.
CC -!- TISSUE SPECIFICITY: Widely expressed. Highest expression in brain,
CC kidney and testis (at protein level). Expressed in adipose tissue (at
CC protein level). {ECO:0000250|UniProtKB:Q8BH82}.
CC -!- SIMILARITY: Belongs to the NAPE-PLD family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=N-acyl phosphatidylethanolamine-
CC specific phospholipase D entry;
CC URL="https://en.wikipedia.org/wiki/N-acyl_phosphatidylethanolamine-specific_phospholipase_D";
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DR EMBL; AY357337; AAR13673.1; -; mRNA.
DR EMBL; AB112352; BAD02399.1; -; mRNA.
DR EMBL; CR936639; CAI56779.1; -; mRNA.
DR EMBL; CH471070; EAW83314.1; -; Genomic_DNA.
DR EMBL; BC071604; AAH71604.1; -; mRNA.
DR CCDS; CCDS5729.1; -.
DR RefSeq; NP_001116310.1; NM_001122838.1.
DR RefSeq; NP_945341.3; NM_198990.4.
DR RefSeq; XP_005250271.2; XM_005250214.4.
DR RefSeq; XP_005250272.1; XM_005250215.2.
DR RefSeq; XP_005250275.1; XM_005250218.2.
DR RefSeq; XP_011514235.1; XM_011515933.2.
DR RefSeq; XP_016867343.1; XM_017011854.1.
DR RefSeq; XP_016867344.1; XM_017011855.1.
DR PDB; 4QN9; X-ray; 2.65 A; A/B=1-393.
DR PDBsum; 4QN9; -.
DR AlphaFoldDB; Q6IQ20; -.
DR SMR; Q6IQ20; -.
DR BioGRID; 128793; 4.
DR DIP; DIP-61398N; -.
DR IntAct; Q6IQ20; 1.
DR STRING; 9606.ENSP00000407112; -.
DR BindingDB; Q6IQ20; -.
DR ChEMBL; CHEMBL4630839; -.
DR DrugBank; DB14009; Medical Cannabis.
DR GuidetoPHARMACOLOGY; 1398; -.
DR SwissLipids; SLP:000001132; -.
DR iPTMnet; Q6IQ20; -.
DR PhosphoSitePlus; Q6IQ20; -.
DR BioMuta; NAPEPLD; -.
DR DMDM; 167016292; -.
DR EPD; Q6IQ20; -.
DR jPOST; Q6IQ20; -.
DR MassIVE; Q6IQ20; -.
DR MaxQB; Q6IQ20; -.
DR PaxDb; Q6IQ20; -.
DR PeptideAtlas; Q6IQ20; -.
DR PRIDE; Q6IQ20; -.
DR ProteomicsDB; 66476; -.
DR Antibodypedia; 16885; 185 antibodies from 23 providers.
DR DNASU; 222236; -.
DR Ensembl; ENST00000341533.8; ENSP00000340093.4; ENSG00000161048.12.
DR Ensembl; ENST00000417955.5; ENSP00000407112.1; ENSG00000161048.12.
DR Ensembl; ENST00000422589.5; ENSP00000412376.1; ENSG00000161048.12.
DR Ensembl; ENST00000427257.5; ENSP00000392775.1; ENSG00000161048.12.
DR Ensembl; ENST00000465647.6; ENSP00000419188.1; ENSG00000161048.12.
DR Ensembl; ENST00000611100.2; ENSP00000482162.1; ENSG00000275723.4.
DR Ensembl; ENST00000622712.4; ENSP00000481285.1; ENSG00000275723.4.
DR Ensembl; ENST00000632159.1; ENSP00000488504.1; ENSG00000275723.4.
DR Ensembl; ENST00000632703.1; ENSP00000488648.1; ENSG00000275723.4.
DR Ensembl; ENST00000633783.1; ENSP00000487770.1; ENSG00000275723.4.
DR GeneID; 222236; -.
DR KEGG; hsa:222236; -.
DR MANE-Select; ENST00000465647.6; ENSP00000419188.1; NM_001122838.3; NP_001116310.1.
DR UCSC; uc003vbc.3; human.
DR CTD; 222236; -.
DR DisGeNET; 222236; -.
DR GeneCards; NAPEPLD; -.
DR HGNC; HGNC:21683; NAPEPLD.
DR HPA; ENSG00000161048; Low tissue specificity.
DR MIM; 612334; gene.
DR neXtProt; NX_Q6IQ20; -.
DR OpenTargets; ENSG00000161048; -.
DR PharmGKB; PA162396960; -.
DR VEuPathDB; HostDB:ENSG00000161048; -.
DR eggNOG; KOG3798; Eukaryota.
DR GeneTree; ENSGT00390000017990; -.
DR HOGENOM; CLU_020884_2_1_1; -.
DR InParanoid; Q6IQ20; -.
DR OMA; QHWTRRT; -.
DR OrthoDB; 1194556at2759; -.
DR PhylomeDB; Q6IQ20; -.
DR TreeFam; TF313520; -.
DR BioCyc; MetaCyc:ENSG00000161048-MON; -.
DR BRENDA; 3.1.4.54; 2681.
DR PathwayCommons; Q6IQ20; -.
DR Reactome; R-HSA-2466712; Biosynthesis of A2E, implicated in retinal degradation.
DR SignaLink; Q6IQ20; -.
DR BioGRID-ORCS; 222236; 5 hits in 1076 CRISPR screens.
DR ChiTaRS; NAPEPLD; human.
DR GenomeRNAi; 222236; -.
DR Pharos; Q6IQ20; Tbio.
DR PRO; PR:Q6IQ20; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q6IQ20; protein.
DR Bgee; ENSG00000161048; Expressed in corpus callosum and 103 other tissues.
DR ExpressionAtlas; Q6IQ20; baseline and differential.
DR Genevisible; Q6IQ20; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005769; C:early endosome; ISS:UniProtKB.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043227; C:membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0005635; C:nuclear envelope; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISS:UniProtKB.
DR GO; GO:0042622; C:photoreceptor outer segment membrane; TAS:Reactome.
DR GO; GO:0032052; F:bile acid binding; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0102200; F:N-acetylphosphatidylethanolamine-hydrolysing phospholipase activity; IEA:UniProtKB-EC.
DR GO; GO:0070290; F:N-acylphosphatidylethanolamine-specific phospholipase D activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0048874; P:host-mediated regulation of intestinal microbiota composition; ISS:UniProtKB.
DR GO; GO:0070291; P:N-acylethanolamine metabolic process; IBA:GO_Central.
DR GO; GO:0070292; P:N-acylphosphatidylethanolamine metabolic process; IDA:UniProtKB.
DR GO; GO:0009395; P:phospholipid catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0090336; P:positive regulation of brown fat cell differentiation; ISS:UniProtKB.
DR GO; GO:0050729; P:positive regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:0001523; P:retinoid metabolic process; TAS:Reactome.
DR GO; GO:0001659; P:temperature homeostasis; ISS:UniProtKB.
DR Gene3D; 3.60.15.10; -; 1.
DR InterPro; IPR001279; Metallo-B-lactamas.
DR InterPro; IPR024884; NAPE-PLD.
DR InterPro; IPR036866; RibonucZ/Hydroxyglut_hydro.
DR Pfam; PF12706; Lactamase_B_2; 1.
DR PIRSF; PIRSF038896; NAPE-PLD; 1.
DR SUPFAM; SSF56281; SSF56281; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Endosome; Golgi apparatus; Hydrolase;
KW Lipid degradation; Lipid metabolism; Membrane; Metal-binding; Nucleus;
KW Phospholipid degradation; Phospholipid metabolism; Reference proteome;
KW Zinc.
FT CHAIN 1..393
FT /note="N-acyl-phosphatidylethanolamine-hydrolyzing
FT phospholipase D"
FT /id="PRO_0000318159"
FT REGION 1..40
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..39
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 185
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:25684574"
FT BINDING 187
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:25684574"
FT BINDING 188
FT /ligand="N-acyl-1,2-diacyl-sn-glycero-3-
FT phosphoethanolamine"
FT /ligand_id="ChEBI:CHEBI:62537"
FT /evidence="ECO:0000305|PubMed:25684574"
FT BINDING 189
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:25684574"
FT BINDING 190
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:25684574"
FT BINDING 253
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:25684574"
FT BINDING 256
FT /ligand="deoxycholate"
FT /ligand_id="ChEBI:CHEBI:23614"
FT /evidence="ECO:0000269|PubMed:25684574,
FT ECO:0007744|PDB:4QN9"
FT BINDING 260
FT /ligand="deoxycholate"
FT /ligand_id="ChEBI:CHEBI:23614"
FT /evidence="ECO:0000269|PubMed:25684574,
FT ECO:0007744|PDB:4QN9"
FT BINDING 284
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:25684574"
FT BINDING 284
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:25684574"
FT BINDING 321
FT /ligand="N-acyl-1,2-diacyl-sn-glycero-3-
FT phosphoethanolamine"
FT /ligand_id="ChEBI:CHEBI:62537"
FT /evidence="ECO:0000305|PubMed:25684574"
FT BINDING 343
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:25684574"
FT BINDING 348
FT /ligand="deoxycholate"
FT /ligand_id="ChEBI:CHEBI:23614"
FT /evidence="ECO:0000269|PubMed:25684574,
FT ECO:0007744|PDB:4QN9"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT VARIANT 152
FT /note="S -> A (almost no change in activity;
FT dbSNP:rs12540583)"
FT /evidence="ECO:0000269|PubMed:16527816"
FT /id="VAR_038695"
FT VARIANT 389
FT /note="D -> N (almost no change in activity;
FT dbSNP:rs3181009)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:16527816, ECO:0000269|PubMed:17974005,
FT ECO:0000269|Ref.4"
FT /id="VAR_038694"
FT MUTAGEN 158
FT /note="Q->S: Impairs homodimerization resulting in loss of
FT activity; when associated with S-159."
FT /evidence="ECO:0000269|PubMed:25684574"
FT MUTAGEN 159
FT /note="Y->S: Impairs homodimerization resulting in loss of
FT activity; when associated with S-158."
FT /evidence="ECO:0000269|PubMed:25684574"
FT MUTAGEN 207
FT /note="L->F: Loss of activity."
FT /evidence="ECO:0000269|PubMed:16527816"
FT MUTAGEN 257
FT /note="R->A: Impairs binding to bile acids resulting in
FT loss of activity."
FT /evidence="ECO:0000269|PubMed:25684574"
FT MUTAGEN 380
FT /note="H->R: Loss of activity."
FT /evidence="ECO:0000269|PubMed:16527816"
FT CONFLICT 281
FT /note="Missing (in Ref. 3; CAI56779)"
FT /evidence="ECO:0000305"
FT CONFLICT 371
FT /note="N -> Y (in Ref. 3; CAI56779)"
FT /evidence="ECO:0000305"
FT STRAND 65..68
FT /evidence="ECO:0007829|PDB:4QN9"
FT HELIX 97..103
FT /evidence="ECO:0007829|PDB:4QN9"
FT TURN 110..113
FT /evidence="ECO:0007829|PDB:4QN9"
FT STRAND 121..123
FT /evidence="ECO:0007829|PDB:4QN9"
FT STRAND 126..129
FT /evidence="ECO:0007829|PDB:4QN9"
FT STRAND 135..139
FT /evidence="ECO:0007829|PDB:4QN9"
FT STRAND 142..147
FT /evidence="ECO:0007829|PDB:4QN9"
FT STRAND 151..153
FT /evidence="ECO:0007829|PDB:4QN9"
FT STRAND 158..161
FT /evidence="ECO:0007829|PDB:4QN9"
FT STRAND 178..182
FT /evidence="ECO:0007829|PDB:4QN9"
FT TURN 188..190
FT /evidence="ECO:0007829|PDB:4QN9"
FT HELIX 193..202
FT /evidence="ECO:0007829|PDB:4QN9"
FT STRAND 207..212
FT /evidence="ECO:0007829|PDB:4QN9"
FT HELIX 216..221
FT /evidence="ECO:0007829|PDB:4QN9"
FT STRAND 226..230
FT /evidence="ECO:0007829|PDB:4QN9"
FT STRAND 235..238
FT /evidence="ECO:0007829|PDB:4QN9"
FT STRAND 241..249
FT /evidence="ECO:0007829|PDB:4QN9"
FT STRAND 257..260
FT /evidence="ECO:0007829|PDB:4QN9"
FT STRAND 269..273
FT /evidence="ECO:0007829|PDB:4QN9"
FT STRAND 278..281
FT /evidence="ECO:0007829|PDB:4QN9"
FT HELIX 291..297
FT /evidence="ECO:0007829|PDB:4QN9"
FT STRAND 301..307
FT /evidence="ECO:0007829|PDB:4QN9"
FT HELIX 314..317
FT /evidence="ECO:0007829|PDB:4QN9"
FT TURN 318..320
FT /evidence="ECO:0007829|PDB:4QN9"
FT HELIX 324..333
FT /evidence="ECO:0007829|PDB:4QN9"
FT STRAND 339..347
FT /evidence="ECO:0007829|PDB:4QN9"
FT STRAND 350..352
FT /evidence="ECO:0007829|PDB:4QN9"
FT HELIX 356..368
FT /evidence="ECO:0007829|PDB:4QN9"
FT TURN 372..374
FT /evidence="ECO:0007829|PDB:4QN9"
FT STRAND 383..385
FT /evidence="ECO:0007829|PDB:4QN9"
SQ SEQUENCE 393 AA; 45596 MW; 5CE3114CC557B698 CRC64;
MDENESNQSL MTSSQYPKEA VRKRQNSARN SGASDSSRFS RKSFKLDYRL EEDVTKSKKG
KDGRFVNPWP TWKNPSIPNV LRWLIMEKDH SSVPSSKEEL DKELPVLKPY FITNPEEAGV
REAGLRVTWL GHATVMVEMD ELIFLTDPIF SSRASPSQYM GPKRFRRSPC TISELPPIDA
VLISHNHYDH LDYNSVIALN ERFGNELRWF VPLGLLDWMQ KCGCENVIEL DWWEENCVPG
HDKVTFVFTP SQHWCKRTLM DDNKVLWGSW SVLGPWNRFF FAGDTGYCPA FEEIGKRFGP
FDLAAIPIGA YEPRWFMKYQ HVDPEEAVRI HTDVQTKKSM AIHWGTFALA NEHYLEPPVK
LNEALERYGL NAEDFFVLKH GESRYLNNDD ENF
