P20D1_MOUSE
ID P20D1_MOUSE Reviewed; 503 AA.
AC Q8C165; Q3UNX0; Q8R117;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=N-fatty-acyl-amino acid synthase/hydrolase PM20D1 {ECO:0000305|PubMed:27374330};
DE EC=3.5.1.114 {ECO:0000269|PubMed:27374330, ECO:0000269|PubMed:29533650, ECO:0000269|PubMed:29967167, ECO:0000269|PubMed:32271712, ECO:0000269|PubMed:32402239};
DE EC=3.5.1.14 {ECO:0000269|PubMed:27374330, ECO:0000269|PubMed:29967167, ECO:0000269|PubMed:32271712, ECO:0000269|PubMed:32402239};
DE AltName: Full=Peptidase M20 domain-containing protein 1 {ECO:0000303|PubMed:27374330, ECO:0000303|PubMed:29967167, ECO:0000312|MGI:MGI:2442939};
DE Short=PM20D1 {ECO:0000303|PubMed:29967167};
DE Flags: Precursor;
GN Name=Pm20d1 {ECO:0000312|MGI:MGI:2442939};
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 [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Kidney, and Skin;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Kidney, Liver, Lung, Pancreas, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, INDUCTION, AND MUTAGENESIS OF HIS-125; ASP-127 AND HIS-465.
RX PubMed=27374330; DOI=10.1016/j.cell.2016.05.071;
RA Long J.Z., Svensson K.J., Bateman L.A., Lin H., Kamenecka T.,
RA Lokurkar I.A., Lou J., Rao R.R., Chang M.R., Jedrychowski M.P., Paulo J.A.,
RA Gygi S.P., Griffin P.R., Nomura D.K., Spiegelman B.M.;
RT "The secreted enzyme PM20D1 regulates lipidated amino acid uncouplers of
RT mitochondria.";
RL Cell 166:424-435(2016).
RN [5]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=29533650; DOI=10.1021/acs.jmedchem.8b00029;
RA Lin H., Long J.Z., Roche A.M., Svensson K.J., Dou F.Y., Chang M.R.,
RA Strutzenberg T., Ruiz C., Cameron M.D., Novick S.J., Berdan C.A.,
RA Louie S.M., Nomura D.K., Spiegelman B.M., Griffin P.R., Kamenecka T.M.;
RT "Discovery of Hydrolysis-Resistant Isoindoline N-Acyl Amino Acid Analogues
RT that Stimulate Mitochondrial Respiration.";
RL J. Med. Chem. 61:3224-3230(2018).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=29967167; DOI=10.1073/pnas.1803389115;
RA Long J.Z., Roche A.M., Berdan C.A., Louie S.M., Roberts A.J.,
RA Svensson K.J., Dou F.Y., Bateman L.A., Mina A.I., Deng Z.,
RA Jedrychowski M.P., Lin H., Kamenecka T.M., Asara J.M., Griffin P.R.,
RA Banks A.S., Nomura D.K., Spiegelman B.M.;
RT "Ablation of PM20D1 reveals N-acyl amino acid control of metabolism and
RT nociception.";
RL Proc. Natl. Acad. Sci. U.S.A. 115:E6937-E6945(2018).
RN [7]
RP FUNCTION, AND INDUCTION.
RX PubMed=31659023; DOI=10.1073/pnas.1913199116;
RA Benson K.K., Hu W., Weller A.H., Bennett A.H., Chen E.R., Khetarpal S.A.,
RA Yoshino S., Bone W.P., Wang L., Rabinowitz J.D., Voight B.F., Soccio R.E.;
RT "Natural human genetic variation determines basal and inducible expression
RT of PM20D1, an obesity-associated gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 116:23232-23242(2019).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBCELLULAR LOCATION, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=32271712; DOI=10.7554/elife.55211;
RA Kim J.T., Terrell S.M., Li V.L., Wei W., Fischer C.R., Long J.Z.;
RT "Cooperative enzymatic control of N-acyl amino acids by PM20D1 and FAAH.";
RL Elife 9:0-0(2020).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, PATHWAY, AND SUBCELLULAR
RP LOCATION.
RX PubMed=32402239; DOI=10.1016/j.chembiol.2020.04.009;
RA Kim J.T., Jedrychowski M.P., Wei W., Fernandez D., Fischer C.R.,
RA Banik S.M., Spiegelman B.M., Long J.Z.;
RT "A Plasma Protein Network Regulates PM20D1 and N-Acyl Amino Acid
RT Bioactivity.";
RL Cell Chem. Biol. 0:0-0(2020).
CC -!- FUNCTION: Secreted enzyme that regulates the endogenous N-fatty acyl
CC amino acid (NAAs) tissue and circulating levels by functioning as a
CC bidirectional NAA synthase/hydrolase. It condenses free fatty acids and
CC free amino acids to generate NAAs and bidirectionally catalyzes the
CC reverse hydrolysis reaction (PubMed:27374330, PubMed:29533650,
CC PubMed:29967167, PubMed:32271712, PubMed:32402239) (Probable). Some of
CC these NAAs stimulate oxidative metabolism via mitochondrial uncoupling,
CC increasing energy expenditure in a UPC1-independent manner. Thereby,
CC this secreted protein may indirectly regulate whole body energy
CC expenditure (PubMed:27374330, PubMed:29967167, PubMed:32271712). PM20D1
CC circulates in tight association with both low- and high-density (LDL
CC and HDL,respectively) lipoprotein particles (PubMed:32402239).
CC {ECO:0000269|PubMed:27374330, ECO:0000269|PubMed:29533650,
CC ECO:0000269|PubMed:29967167, ECO:0000269|PubMed:32271712,
CC ECO:0000269|PubMed:32402239, ECO:0000305|PubMed:31659023}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an N-acyl-L-amino acid + H2O = a carboxylate + an L-alpha-
CC amino acid; Xref=Rhea:RHEA:15565, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:29067, ChEBI:CHEBI:59869, ChEBI:CHEBI:59874; EC=3.5.1.14;
CC Evidence={ECO:0000269|PubMed:27374330, ECO:0000269|PubMed:29967167,
CC ECO:0000269|PubMed:32271712, ECO:0000269|PubMed:32402239};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15566;
CC Evidence={ECO:0000269|PubMed:27374330, ECO:0000269|PubMed:29967167,
CC ECO:0000269|PubMed:32271712, ECO:0000269|PubMed:32402239};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:15567;
CC Evidence={ECO:0000269|PubMed:27374330, ECO:0000269|PubMed:32271712};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an N-acyl-aromatic L-alpha-amino acid + H2O = a carboxylate +
CC an aromatic L-alpha-amino acid; Xref=Rhea:RHEA:54184,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:29067, ChEBI:CHEBI:84824,
CC ChEBI:CHEBI:138093; EC=3.5.1.114;
CC Evidence={ECO:0000269|PubMed:27374330, ECO:0000269|PubMed:29533650,
CC ECO:0000269|PubMed:29967167, ECO:0000269|PubMed:32271712,
CC ECO:0000269|PubMed:32402239};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54185;
CC Evidence={ECO:0000269|PubMed:27374330, ECO:0000269|PubMed:29533650,
CC ECO:0000269|PubMed:29967167, ECO:0000269|PubMed:32271712};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:54186;
CC Evidence={ECO:0000269|PubMed:27374330, ECO:0000269|PubMed:29967167,
CC ECO:0000269|PubMed:32271712, ECO:0000269|PubMed:32402239};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-glycine =
CC (5Z,8Z,11Z,14Z)-eicosatetraenoate + glycine; Xref=Rhea:RHEA:64108,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:32395, ChEBI:CHEBI:57305,
CC ChEBI:CHEBI:59002; Evidence={ECO:0000269|PubMed:29967167,
CC ECO:0000269|PubMed:32271712, ECO:0000269|PubMed:32402239};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64109;
CC Evidence={ECO:0000269|PubMed:29967167, ECO:0000269|PubMed:32271712,
CC ECO:0000269|PubMed:32402239};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:64110;
CC Evidence={ECO:0000269|PubMed:32271712};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-hexadecanoyl-L-phenylalanine = hexadecanoate + L-
CC phenylalanine; Xref=Rhea:RHEA:64124, ChEBI:CHEBI:7896,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:58095, ChEBI:CHEBI:149699;
CC Evidence={ECO:0000269|PubMed:32271712};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64125;
CC Evidence={ECO:0000269|PubMed:32271712};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-octadecanoyl-L-phenylalanine = L-phenylalanine +
CC octadecanoate; Xref=Rhea:RHEA:64128, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:25629, ChEBI:CHEBI:58095, ChEBI:CHEBI:149700;
CC Evidence={ECO:0000269|PubMed:32271712};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64129;
CC Evidence={ECO:0000269|PubMed:32271712};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-L-
CC phenylalanine = (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + L-
CC phenylalanine; Xref=Rhea:RHEA:64132, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:58095, ChEBI:CHEBI:77016, ChEBI:CHEBI:149701;
CC Evidence={ECO:0000269|PubMed:32271712};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64133;
CC Evidence={ECO:0000269|PubMed:32271712};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(9Z-octadecenoyl)-L-asparagine = (9Z)-octadecenoate +
CC L-asparagine; Xref=Rhea:RHEA:64136, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:30823, ChEBI:CHEBI:58048, ChEBI:CHEBI:149730;
CC Evidence={ECO:0000269|PubMed:32271712};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64137;
CC Evidence={ECO:0000269|PubMed:32271712};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z)-octadecenoate + glycine = H2O + N-(9Z-
CC octadecenoyl)glycine; Xref=Rhea:RHEA:51316, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:30823, ChEBI:CHEBI:57305, ChEBI:CHEBI:133992;
CC Evidence={ECO:0000269|PubMed:27374330, ECO:0000269|PubMed:32271712};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:51318;
CC Evidence={ECO:0000269|PubMed:27374330, ECO:0000269|PubMed:32271712};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(9Z-octadecenoyl)-L-lysine = (9Z)-octadecenoate + L-
CC lysine; Xref=Rhea:RHEA:64192, ChEBI:CHEBI:15377, ChEBI:CHEBI:30823,
CC ChEBI:CHEBI:32551, ChEBI:CHEBI:149731;
CC Evidence={ECO:0000269|PubMed:32271712};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64193;
CC Evidence={ECO:0000269|PubMed:32271712};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(9Z-octadecenoyl)-L-methionine = (9Z)-octadecenoate +
CC L-methionine; Xref=Rhea:RHEA:64144, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:30823, ChEBI:CHEBI:57844, ChEBI:CHEBI:149732;
CC Evidence={ECO:0000269|PubMed:32271712};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64145;
CC Evidence={ECO:0000269|PubMed:32271712};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(9Z-octadecenoyl)-L-serine = (9Z)-octadecenoate + L-
CC serine; Xref=Rhea:RHEA:51352, ChEBI:CHEBI:15377, ChEBI:CHEBI:30823,
CC ChEBI:CHEBI:33384, ChEBI:CHEBI:134031;
CC Evidence={ECO:0000269|PubMed:27374330, ECO:0000269|PubMed:32271712};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51353;
CC Evidence={ECO:0000269|PubMed:27374330, ECO:0000269|PubMed:32271712};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(9Z-octadecenoyl)-L-tryptophan = (9Z)-octadecenoate +
CC L-tryptophan; Xref=Rhea:RHEA:64176, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:30823, ChEBI:CHEBI:57912, ChEBI:CHEBI:149733;
CC Evidence={ECO:0000269|PubMed:32271712};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64177;
CC Evidence={ECO:0000269|PubMed:32271712};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(9Z-octadecenoyl)-L-tyrosine = (9Z)-octadecenoate + L-
CC tyrosine; Xref=Rhea:RHEA:64184, ChEBI:CHEBI:15377, ChEBI:CHEBI:30823,
CC ChEBI:CHEBI:58315, ChEBI:CHEBI:149734;
CC Evidence={ECO:0000269|PubMed:32271712};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64185;
CC Evidence={ECO:0000269|PubMed:32271712};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(9Z-octadecenoyl)-L-glutamine = (9Z)-octadecenoate +
CC L-glutamine; Xref=Rhea:RHEA:51356, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:30823, ChEBI:CHEBI:58359, ChEBI:CHEBI:134033;
CC Evidence={ECO:0000269|PubMed:27374330, ECO:0000269|PubMed:32271712};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51357;
CC Evidence={ECO:0000269|PubMed:27374330, ECO:0000269|PubMed:32271712};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-L-serine =
CC (5Z,8Z,11Z,14Z)-eicosatetraenoate + L-serine; Xref=Rhea:RHEA:64116,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:32395, ChEBI:CHEBI:33384,
CC ChEBI:CHEBI:149697; Evidence={ECO:0000269|PubMed:32271712};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64117;
CC Evidence={ECO:0000269|PubMed:32271712};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:64118;
CC Evidence={ECO:0000269|PubMed:32271712};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + L-phenylalanine = H2O + N-
CC (5Z,8Z,11Z,14Z-eicosatetraenoyl)-L-phenylalanine;
CC Xref=Rhea:RHEA:51312, ChEBI:CHEBI:15377, ChEBI:CHEBI:32395,
CC ChEBI:CHEBI:58095, ChEBI:CHEBI:134022;
CC Evidence={ECO:0000269|PubMed:32271712};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51313;
CC Evidence={ECO:0000269|PubMed:32271712};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:51314;
CC Evidence={ECO:0000269|PubMed:32271712};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(9Z-octadecenoyl)-L-leucine = (9Z)-octadecenoate + L-
CC leucine; Xref=Rhea:RHEA:51360, ChEBI:CHEBI:15377, ChEBI:CHEBI:30823,
CC ChEBI:CHEBI:57427, ChEBI:CHEBI:134035;
CC Evidence={ECO:0000269|PubMed:27374330};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51361;
CC Evidence={ECO:0000269|PubMed:27374330};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:51362;
CC Evidence={ECO:0000269|PubMed:27374330};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z)-octadecenoate + L-phenylalanine = H2O + N-(9Z-
CC octadecenoyl)-L-phenylalanine; Xref=Rhea:RHEA:51300,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:30823, ChEBI:CHEBI:58095,
CC ChEBI:CHEBI:134020; Evidence={ECO:0000269|PubMed:27374330,
CC ECO:0000269|PubMed:29533650, ECO:0000269|PubMed:29967167,
CC ECO:0000269|PubMed:32402239};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51301;
CC Evidence={ECO:0000269|PubMed:27374330, ECO:0000269|PubMed:29967167,
CC ECO:0000269|PubMed:32402239};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:51302;
CC Evidence={ECO:0000269|PubMed:27374330, ECO:0000269|PubMed:29533650,
CC ECO:0000269|PubMed:29967167};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000250};
CC -!- ACTIVITY REGULATION: Lipoproteins are powerful coactivators of PM20D1
CC activity in vitro and NAA biosynthesis in vivo.
CC {ECO:0000269|PubMed:32402239}.
CC -!- PATHWAY: Amino-acid metabolism. {ECO:0000269|PubMed:27374330,
CC ECO:0000269|PubMed:29967167, ECO:0000269|PubMed:32271712,
CC ECO:0000269|PubMed:32402239}.
CC -!- PATHWAY: Energy metabolism; electron transfer.
CC {ECO:0000269|PubMed:27374330, ECO:0000269|PubMed:29967167,
CC ECO:0000269|PubMed:32271712}.
CC -!- PATHWAY: Lipid metabolism; fatty acid metabolism.
CC {ECO:0000269|PubMed:27374330, ECO:0000269|PubMed:29967167,
CC ECO:0000269|PubMed:32271712, ECO:0000269|PubMed:32402239}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:27374330,
CC ECO:0000269|PubMed:32271712, ECO:0000269|PubMed:32402239}.
CC -!- TISSUE SPECIFICITY: In addition to being detected in blood (at protein
CC level), PM20D1 is also highly expressed in other tissues including
CC brown adipocytes, liver and kidney (PubMed:27374330, PubMed:29967167).
CC It is also expressed in small intestine, large intestine, heart and
CC pancreas (PubMed:29967167). {ECO:0000269|PubMed:27374330,
CC ECO:0000269|PubMed:29967167}.
CC -!- INDUCTION: Up-regulated in adipose tissue upon cold exposure.
CC {ECO:0000269|PubMed:27374330, ECO:0000269|PubMed:31659023}.
CC -!- DISRUPTION PHENOTYPE: Genetic ablation causes tissue-specific
CC bidirectional dysregulation of several N-acyl amino acids
CC (PubMed:29967167, PubMed:32271712). Locomotor activity and resting
CC energy requirements (RER) are slightly increased and decreased,
CC respectively, in PM20D1-KO mice on chow diet, while diet-induced
CC obesity conditions produce a marked impairment in glucose homeostasis
CC and insulin sensitivity in these mice. They also exhibit enhanced
CC defense of body temperature in cold, and antinociceptive behaviors
CC selectively in response to chemical and inflammatory pain stimuli while
CC maintaining normal thermal pain sensation and normal movement
CC (PubMed:29967167). {ECO:0000269|PubMed:29967167,
CC ECO:0000269|PubMed:32271712}.
CC -!- MISCELLANEOUS: Overexpression in mice blunts high fat diet-induced
CC increase in fat mass and associated weight gain (PubMed:27374330). Free
CC NAAs represent the biologically active form of these circulating
CC molecules, and the circulating NAAs bioactivity is determined by plasma
CC protein binding (PubMed:32402239). {ECO:0000269|PubMed:27374330,
CC ECO:0000269|PubMed:32402239}.
CC -!- SIMILARITY: Belongs to the peptidase M20A family. {ECO:0000305}.
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DR EMBL; AK028883; BAC26171.1; -; mRNA.
DR EMBL; AK143953; BAE25627.1; -; mRNA.
DR EMBL; BC025830; AAH25830.1; -; mRNA.
DR EMBL; BC120725; AAI20726.1; -; mRNA.
DR EMBL; BC125395; AAI25396.1; -; mRNA.
DR CCDS; CCDS15274.1; -.
DR RefSeq; NP_835180.2; NM_178079.3.
DR RefSeq; XP_006529401.1; XM_006529338.3.
DR AlphaFoldDB; Q8C165; -.
DR SMR; Q8C165; -.
DR IntAct; Q8C165; 1.
DR STRING; 10090.ENSMUSP00000108012; -.
DR ChEMBL; CHEMBL4295889; -.
DR SwissLipids; SLP:000001659; -.
DR MEROPS; M20.011; -.
DR CarbonylDB; Q8C165; -.
DR GlyConnect; 2603; 2 N-Linked glycans (2 sites).
DR GlyGen; Q8C165; 2 sites, 2 N-linked glycans (2 sites).
DR iPTMnet; Q8C165; -.
DR PhosphoSitePlus; Q8C165; -.
DR SwissPalm; Q8C165; -.
DR CPTAC; non-CPTAC-3475; -.
DR jPOST; Q8C165; -.
DR MaxQB; Q8C165; -.
DR PaxDb; Q8C165; -.
DR PeptideAtlas; Q8C165; -.
DR PRIDE; Q8C165; -.
DR ProteomicsDB; 294087; -.
DR Antibodypedia; 2556; 26 antibodies from 12 providers.
DR DNASU; 212933; -.
DR Ensembl; ENSMUST00000048660; ENSMUSP00000046079; ENSMUSG00000042251.
DR Ensembl; ENSMUST00000112393; ENSMUSP00000108012; ENSMUSG00000042251.
DR GeneID; 212933; -.
DR KEGG; mmu:212933; -.
DR UCSC; uc007cnt.2; mouse.
DR CTD; 148811; -.
DR MGI; MGI:2442939; Pm20d1.
DR VEuPathDB; HostDB:ENSMUSG00000042251; -.
DR eggNOG; KOG2275; Eukaryota.
DR GeneTree; ENSGT00940000156659; -.
DR HOGENOM; CLU_021802_11_1_1; -.
DR InParanoid; Q8C165; -.
DR OMA; NYGDHSG; -.
DR OrthoDB; 1432382at2759; -.
DR PhylomeDB; Q8C165; -.
DR TreeFam; TF328688; -.
DR Reactome; R-MMU-9673163; Oleoyl-phe metabolism.
DR UniPathway; UPA00092; -.
DR UniPathway; UPA00199; -.
DR BioGRID-ORCS; 212933; 2 hits in 74 CRISPR screens.
DR PRO; PR:Q8C165; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q8C165; protein.
DR Bgee; ENSMUSG00000042251; Expressed in epithelium of small intestine and 125 other tissues.
DR ExpressionAtlas; Q8C165; baseline and differential.
DR Genevisible; Q8C165; MM.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0004046; F:aminoacylase activity; IEA:UniProtKB-EC.
DR GO; GO:0016811; F:hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides; IDA:UniProtKB.
DR GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008233; F:peptidase activity; IEA:UniProtKB-KW.
DR GO; GO:1990845; P:adaptive thermogenesis; IMP:UniProtKB.
DR GO; GO:0043604; P:amide biosynthetic process; IDA:UniProtKB.
DR GO; GO:0043605; P:cellular amide catabolic process; IDA:UniProtKB.
DR GO; GO:0006520; P:cellular amino acid metabolic process; IDA:UniProtKB.
DR GO; GO:0044255; P:cellular lipid metabolic process; IDA:UniProtKB.
DR GO; GO:0097009; P:energy homeostasis; IMP:UniProtKB.
DR GO; GO:0006631; P:fatty acid metabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:1901215; P:negative regulation of neuron death; ISO:MGI.
DR GO; GO:0006807; P:nitrogen compound metabolic process; IBA:GO_Central.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:2000275; P:regulation of oxidative phosphorylation uncoupler activity; IMP:UniProtKB.
DR GO; GO:0022904; P:respiratory electron transport chain; IEA:UniProtKB-UniPathway.
DR InterPro; IPR036264; Bact_exopeptidase_dim_dom.
DR InterPro; IPR002933; Peptidase_M20.
DR InterPro; IPR011650; Peptidase_M20_dimer.
DR Pfam; PF07687; M20_dimer; 1.
DR Pfam; PF01546; Peptidase_M20; 1.
DR SUPFAM; SSF55031; SSF55031; 1.
PE 1: Evidence at protein level;
KW Glycoprotein; Hydrolase; Lipid metabolism; Lyase; Metal-binding; Protease;
KW Reference proteome; Secreted; Signal; Zinc.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..503
FT /note="N-fatty-acyl-amino acid synthase/hydrolase PM20D1"
FT /id="PRO_0000321929"
FT ACT_SITE 127
FT /evidence="ECO:0000250"
FT ACT_SITE 191
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 125
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 157
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 157
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 192
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 218
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 465
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT CARBOHYD 72
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 443
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 125
FT /note="H->A: Loss of N-fatty-acyl-amino acid
FT synthase/hydrolase activity."
FT /evidence="ECO:0000269|PubMed:27374330"
FT MUTAGEN 127
FT /note="D->A: Loss of N-fatty-acyl-amino acid
FT synthase/hydrolase activity."
FT /evidence="ECO:0000269|PubMed:27374330"
FT MUTAGEN 465
FT /note="H->A: Loss of N-fatty-acyl-amino acid
FT synthase/hydrolase activity."
FT /evidence="ECO:0000269|PubMed:27374330"
FT CONFLICT 373
FT /note="E -> G (in Ref. 2; BAE25627)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 503 AA; 55663 MW; CD6C87E276E77795 CRC64;
MAELLASLPA WAAVLLLFFA TVSGSTGPRS RENRGASRIP SQFSEEERVA IKEALKGAIQ
IPTVSFSHEE SNTTALAEFG EYIRKAFPTV FHSSLVQHEV VAKYSHLFTI QGSDPSLQPY
MLMAHIDVVP APEEGWEVPP FSGLERNGFI YGRGALDNKN SVMAILHALE LLLIRNYSPK
RSFFIALGHD EEVSGEKGAQ KISALLQARG VQLAFLVDEG SFILEGFIPN LEKPVAMISV
TEKGALDLML QVNMTPGHSS APPKETSIGI LSAAVSRLEQ TPMPNMFGGG PLKKTMKLLA
NEFSFPINIV LRNLWLFHPI VSRIMERNPI TNALVRTTTA LTMFNAGIKV NVIPPLAQAT
INCRIHPSQT VHEVLELVKN TVADDRVQLH VLRSFEPLPI SPSDDQAMGY QLLQETIRSV
FPEVDIVVPG ICIANTDTRH YANITNGMYR FNPLPLNPQD FSGVHGINEK VSVQNYQNQV
KFIFEFIQNA DTYKEPVPHL HEL
