NAPEP_MOUSE
ID NAPEP_MOUSE Reviewed; 396 AA.
AC Q8BH82;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D;
DE Short=N-acyl phosphatidylethanolamine phospholipase D;
DE Short=NAPE-PLD {ECO:0000303|PubMed:25757720};
DE Short=NAPE-hydrolyzing phospholipase D;
DE EC=3.1.4.54 {ECO:0000269|PubMed:14634025};
GN Name=Napepld {ECO:0000312|MGI:MGI:2140885}; Synonyms=Mbldc1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND CATALYTIC
RP ACTIVITY.
RC TISSUE=Brain;
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 [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Adipose tissue, and Hippocampus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; 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 [4]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=15760304; DOI=10.1042/bj20041790;
RA Okamoto Y., Morishita J., Wang J., Schmid P.C., Krebsbach R.J.,
RA Schmid H.H., Ueda N.;
RT "Mammalian cells stably overexpressing N-acylphosphatidylethanolamine-
RT hydrolysing phospholipase D exhibit significantly decreased levels of N-
RT acylphosphatidylethanolamines.";
RL Biochem. J. 389:241-247(2005).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=16605240; DOI=10.1021/bi060163l;
RA Leung D., Saghatelian A., Simon G.M., Cravatt B.F.;
RT "Inactivation of N-acyl phosphatidylethanolamine phospholipase D reveals
RT multiple mechanisms for the biosynthesis of endocannabinoids.";
RL Biochemistry 45:4720-4726(2006).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=17655883; DOI=10.1016/j.neuropharm.2007.06.001;
RA Wang J., Okamoto Y., Tsuboi K., Ueda N.;
RT "The stimulatory effect of phosphatidylethanolamine on N-
RT acylphosphatidylethanolamine-hydrolyzing phospholipase D (NAPE-PLD).";
RL Neuropharmacology 54:8-15(2008).
RN [7]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=21801852; DOI=10.1016/j.bbalip.2011.07.009;
RA Tsuboi K., Okamoto Y., Ikematsu N., Inoue M., Shimizu Y., Uyama T.,
RA Wang J., Deutsch D.G., Burns M.P., Ulloa N.M., Tokumura A., Ueda N.;
RT "Enzymatic formation of N-acylethanolamines from N-acylethanolamine
RT plasmalogen through N-acylphosphatidylethanolamine-hydrolyzing
RT phospholipase D-dependent and -independent pathways.";
RL Biochim. Biophys. Acta 1811:565-577(2011).
RN [8]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=25757720; DOI=10.1038/ncomms7495;
RA Geurts L., Everard A., Van Hul M., Essaghir A., Duparc T., Matamoros S.,
RA Plovier H., Castel J., Denis R.G., Bergiers M., Druart C., Alhouayek M.,
RA Delzenne N.M., Muccioli G.G., Demoulin J.B., Luquet S., Cani P.D.;
RT "Adipose tissue NAPE-PLD controls fat mass development by altering the
RT browning process and gut microbiota.";
RL Nat. Commun. 6:6495-6495(2015).
RN [9]
RP FUNCTION, AND INDUCTION.
RX PubMed=31685899; DOI=10.1038/s41598-019-51799-1;
RA Palese F., Pontis S., Realini N., Piomelli D.;
RT "A protective role for N-acylphosphatidylethanolamine phospholipase D in 6-
RT OHDA-induced neurodegeneration.";
RL Sci. Rep. 9:15927-15927(2019).
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:15760304, PubMed:17655883,
CC PubMed:21801852). 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 (PubMed:21801852, PubMed:16605240). May control NAPE homeostasis
CC in dopaminergic neuron membranes and regulate neuron survival, partly
CC through RAC1 activation (PubMed:31685899). As a regulator of lipid
CC metabolism in the adipose tissue, mediates the crosstalk between
CC adipocytes, gut microbiota and immune cells to control body temperature
CC and weight. In particular, regulates energy homeostasis by promoting
CC cold-induced brown or beige adipocyte differentiation program to
CC generate heat from fatty acids and glucose (PubMed:25757720). Has
CC limited D-type phospholipase activity toward N-acyl lyso-NAPEs
CC (PubMed:14634025). {ECO:0000269|PubMed:14634025,
CC ECO:0000269|PubMed:15760304, ECO:0000269|PubMed:16605240,
CC ECO:0000269|PubMed:17655883, ECO:0000269|PubMed:21801852,
CC ECO:0000269|PubMed:25757720, ECO:0000269|PubMed:31685899}.
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:15760304};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33160;
CC Evidence={ECO:0000305|PubMed:14634025, ECO:0000305|PubMed:15760304};
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:15760304, ECO:0000269|PubMed:16605240,
CC ECO:0000269|PubMed:17655883, ECO:0000269|PubMed:21801852};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45541;
CC Evidence={ECO:0000305|PubMed:15760304, ECO:0000305|PubMed:16605240,
CC ECO:0000305|PubMed:17655883, ECO:0000305|PubMed:21801852};
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:0000269|PubMed:14634025};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45597;
CC Evidence={ECO:0000305|PubMed:14634025};
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:0000269|PubMed:14634025};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45537;
CC Evidence={ECO:0000305|PubMed:14634025};
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:0000269|PubMed:14634025};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45533;
CC Evidence={ECO:0000305|PubMed:14634025};
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:16605240};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:56549;
CC Evidence={ECO:0000305|PubMed:16605240};
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:0000269|PubMed:14634025};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45529;
CC Evidence={ECO:0000305|PubMed:14634025};
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:0000269|PubMed:21801852};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:56465;
CC Evidence={ECO:0000305|PubMed:21801852};
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:0000269|PubMed:14634025};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53165;
CC Evidence={ECO:0000305|PubMed:14634025};
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:0000269|PubMed:14634025};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45593;
CC Evidence={ECO:0000305|PubMed:14634025};
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:0000269|PubMed:14634025};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45545;
CC Evidence={ECO:0000305|PubMed:14634025};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q6IQ20};
CC Note=Binds 2 zinc divalent cations per subunit.
CC {ECO:0000250|UniProtKB:Q6IQ20};
CC -!- ACTIVITY REGULATION: Activated by divalent cations (PubMed:17655883).
CC Activated by bile acids (By similarity). Activated by membrane
CC phospholipids such as phosphatidylethanolamines (PubMed:17655883).
CC {ECO:0000250|UniProtKB:Q6IQ20, ECO:0000269|PubMed:17655883}.
CC -!- SUBUNIT: Homodimer. Bile acids promote the assembly of inactive
CC monomers into an active dimer and enable catalysis.
CC {ECO:0000250|UniProtKB:Q6IQ20}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:Q6IQ20}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q6IQ20}. Early endosome membrane
CC {ECO:0000250|UniProtKB:Q6IQ20}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q6IQ20}. Nucleus envelope
CC {ECO:0000250|UniProtKB:Q6IQ20}. Nucleus, nucleoplasm
CC {ECO:0000250|UniProtKB:Q6IQ20}. Note=Localized in the proximity of the
CC cellular membranes likely through interaction with membrane
CC phospholipids. {ECO:0000250|UniProtKB:Q6IQ20}.
CC -!- TISSUE SPECIFICITY: Widely expressed. Highest expression in brain,
CC spinal cord, kidney and testis (at protein level) (PubMed:14634025,
CC PubMed:16605240). Expressed in adipose tissue (at protein level)
CC (PubMed:25757720). {ECO:0000269|PubMed:14634025,
CC ECO:0000269|PubMed:16605240, ECO:0000269|PubMed:25757720}.
CC -!- INDUCTION: Down-regulated by neurotoxin 6-hydroxydopamine.
CC {ECO:0000269|PubMed:31685899}.
CC -!- DISRUPTION PHENOTYPE: Knockout mice are born at the expected Mendelian
CC rate (PubMed:16605240). White adipose-tissue specific knockdown
CC (effective when differentiation of adipose tissue is complete) causes
CC obesity, adipose tissue inflammation, insulin resistance in the liver
CC and profound changes of gut microbiota composition.
CC {ECO:0000269|PubMed:16605240, ECO:0000269|PubMed:25757720}.
CC -!- SIMILARITY: Belongs to the NAPE-PLD family. {ECO:0000305}.
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DR EMBL; AB112350; BAD02397.1; -; mRNA.
DR EMBL; AK049135; BAC33563.1; -; mRNA.
DR EMBL; AK080888; BAC38064.1; -; mRNA.
DR EMBL; AK141585; BAE24749.1; -; mRNA.
DR EMBL; BC062890; AAH62890.1; -; mRNA.
DR CCDS; CCDS19105.1; -.
DR RefSeq; NP_848843.1; NM_178728.5.
DR RefSeq; XP_006535774.1; XM_006535711.2.
DR RefSeq; XP_006535775.1; XM_006535712.2.
DR AlphaFoldDB; Q8BH82; -.
DR SMR; Q8BH82; -.
DR STRING; 10090.ENSMUSP00000054458; -.
DR BindingDB; Q8BH82; -.
DR ChEMBL; CHEMBL2163172; -.
DR SwissLipids; SLP:000001130; -.
DR iPTMnet; Q8BH82; -.
DR PhosphoSitePlus; Q8BH82; -.
DR MaxQB; Q8BH82; -.
DR PaxDb; Q8BH82; -.
DR PeptideAtlas; Q8BH82; -.
DR PRIDE; Q8BH82; -.
DR ProteomicsDB; 252766; -.
DR Antibodypedia; 16885; 185 antibodies from 23 providers.
DR Ensembl; ENSMUST00000060899; ENSMUSP00000054458; ENSMUSG00000044968.
DR Ensembl; ENSMUST00000115217; ENSMUSP00000110872; ENSMUSG00000044968.
DR GeneID; 242864; -.
DR KEGG; mmu:242864; -.
DR UCSC; uc008wov.1; mouse.
DR CTD; 222236; -.
DR MGI; MGI:2140885; Napepld.
DR VEuPathDB; HostDB:ENSMUSG00000044968; -.
DR eggNOG; KOG3798; Eukaryota.
DR GeneTree; ENSGT00390000017990; -.
DR HOGENOM; CLU_020884_2_1_1; -.
DR InParanoid; Q8BH82; -.
DR OMA; QHWTRRT; -.
DR OrthoDB; 1194556at2759; -.
DR PhylomeDB; Q8BH82; -.
DR TreeFam; TF313520; -.
DR BRENDA; 3.1.4.54; 3474.
DR BioGRID-ORCS; 242864; 0 hits in 75 CRISPR screens.
DR ChiTaRS; Napepld; mouse.
DR PRO; PR:Q8BH82; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q8BH82; protein.
DR Bgee; ENSMUSG00000044968; Expressed in ascending aorta and 172 other tissues.
DR Genevisible; Q8BH82; MM.
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:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043227; C:membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005635; C:nuclear envelope; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISS:UniProtKB.
DR GO; GO:0032052; F:bile acid binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
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:0004620; F:phospholipase activity; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0048874; P:host-mediated regulation of intestinal microbiota composition; IMP:UniProtKB.
DR GO; GO:0070291; P:N-acylethanolamine metabolic process; IDA:MGI.
DR GO; GO:0070292; P:N-acylphosphatidylethanolamine metabolic process; IDA:UniProtKB.
DR GO; GO:1903999; P:negative regulation of eating behavior; ISO:MGI.
DR GO; GO:0009395; P:phospholipid catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0006644; P:phospholipid metabolic process; ISO:MGI.
DR GO; GO:0090336; P:positive regulation of brown fat cell differentiation; IMP:UniProtKB.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IMP:UniProtKB.
DR GO; GO:0001659; P:temperature homeostasis; IMP: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 Acetylation; Endosome; Golgi apparatus; Hydrolase; Lipid degradation;
KW Lipid metabolism; Membrane; Metal-binding; Nucleus;
KW Phospholipid degradation; Phospholipid metabolism; Reference proteome;
KW Zinc.
FT CHAIN 1..396
FT /note="N-acyl-phosphatidylethanolamine-hydrolyzing
FT phospholipase D"
FT /id="PRO_0000318160"
FT REGION 1..39
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 8..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:0000250|UniProtKB:Q6IQ20"
FT BINDING 187
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q6IQ20"
FT BINDING 188
FT /ligand="N-acyl-1,2-diacyl-sn-glycero-3-
FT phosphoethanolamine"
FT /ligand_id="ChEBI:CHEBI:62537"
FT /evidence="ECO:0000250|UniProtKB:Q6IQ20"
FT BINDING 189
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q6IQ20"
FT BINDING 190
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q6IQ20"
FT BINDING 253
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q6IQ20"
FT BINDING 256
FT /ligand="deoxycholate"
FT /ligand_id="ChEBI:CHEBI:23614"
FT /evidence="ECO:0000250|UniProtKB:Q6IQ20"
FT BINDING 284
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q6IQ20"
FT BINDING 284
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q6IQ20"
FT BINDING 321
FT /ligand="N-acyl-1,2-diacyl-sn-glycero-3-
FT phosphoethanolamine"
FT /ligand_id="ChEBI:CHEBI:62537"
FT /evidence="ECO:0000250|UniProtKB:Q6IQ20"
FT BINDING 343
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q6IQ20"
FT BINDING 348
FT /ligand="deoxycholate"
FT /ligand_id="ChEBI:CHEBI:23614"
FT /evidence="ECO:0000250|UniProtKB:Q6IQ20"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q6IQ20"
SQ SEQUENCE 396 AA; 45816 MW; 432E61F81D441E0A CRC64;
MDEYEDSQSP APSYQYPKET LRKRQNSVQN SGGSVSSRFS RKSFKLDYRL EEDVTKSKKG
KDGRFVNPWP TWKNISIPNV LRWLIMEKNH SGVPGSKEEL DKELPVLKPY FVSDPEDAGV
REAGLRVTWL GHATLMVEMD ELIFLTDPMF SSRASPSQYM GPKRFRRPPC TISELPTIDA
VLISHNHYDH LDYGSVLALN ERFGSELRWF VPLGLLDWMQ KCGCENVIEL DWWEENCVPG
HDKVTFVFTP SQHWCKRTLL DDNKVLWGSW SVLGPWSRFF FAGDTGYCPA FEEIGKRFGP
FDLAAIPIGA YEPRWFMKYQ HADPEDAVRI HIDLQTKRSV AIHWGTFALA NEHYLEPPVK
LNEALERYGL SCEDFFILKH GESRYLNTDD RAFEET
