ID   P20D1_HUMAN             Reviewed;         502 AA.
AC   Q6GTS8; Q6P4E3; Q96DM4;
DT   26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT   11-JAN-2011, sequence version 3.
DT   27-MAR-2024, entry version 146.
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};
DE            EC=3.5.1.14 {ECO:0000269|PubMed:27374330};
DE   AltName: Full=Peptidase M20 domain-containing protein 1 {ECO:0000312|HGNC:HGNC:26518};
DE   Flags: Precursor;
GN   Name=PM20D1 {ECO:0000312|HGNC:HGNC:26518};
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 [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANTS
RP   VAL-149 AND TRP-153.
RC   TISSUE=Kidney, and Spleen;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16710414; DOI=10.1038/nature04727;
RA   Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA   Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA   Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA   Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA   Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA   Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA   Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA   Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA   Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA   Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA   Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA   Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA   Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA   Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA   Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA   Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA   Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA   Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA   McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA   Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA   Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA   Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA   Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA   Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA   White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA   Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA   Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA   Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT   "The DNA sequence and biological annotation of human chromosome 1.";
RL   Nature 441:315-321(2006).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS TYR-33;
RP   VAL-149; TRP-153; THR-237; ARG-346 AND THR-380.
RC   TISSUE=Pancreas, and Skin;
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, CATALYTIC ACTIVITY, AND PATHWAY.
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   MISCELLANEOUS.
RX   PubMed=29736028; DOI=10.1038/s41591-018-0013-y;
RA   Sanchez-Mut J.V., Heyn H., Silva B.A., Dixsaut L., Garcia-Esparcia P.,
RA   Vidal E., Sayols S., Glauser L., Monteagudo-Sanchez A., Perez-Tur J.,
RA   Ferrer I., Monk D., Schneider B., Esteller M., Graeff J.;
RT   "PM20D1 is a quantitative trait locus associated with Alzheimer's
RT   disease.";
RL   Nat. Med. 24:598-603(2018).
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 (PubMed:27374330). It condenses
CC       free fatty acids and free amino acids to generate NAAs and
CC       bidirectionally catalyzes the reverse hydrolysis reaction
CC       (PubMed:27374330). Some of these NAAs stimulate oxidative metabolism
CC       via mitochondrial uncoupling, increasing energy expenditure in a UPC1-
CC       independent manner. Thereby, this secreted protein may indirectly
CC       regulate whole body energy expenditure. PM20D1 circulates in tight
CC       association with both low- and high-density (LDL and HDL,respectively)
CC       lipoprotein particles (By similarity). {ECO:0000250|UniProtKB:Q8C165,
CC       ECO:0000269|PubMed:27374330}.
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};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15566;
CC         Evidence={ECO:0000269|PubMed:27374330};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:15567;
CC         Evidence={ECO:0000269|PubMed:27374330};
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};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54185;
CC         Evidence={ECO:0000269|PubMed:27374330};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:54186;
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       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51301;
CC         Evidence={ECO:0000269|PubMed:27374330};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:51302;
CC         Evidence={ECO:0000269|PubMed:27374330};
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=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:0000250|UniProtKB:Q8C165};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64109;
CC         Evidence={ECO:0000250|UniProtKB:Q8C165};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:64110;
CC         Evidence={ECO:0000250|UniProtKB:Q8C165};
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:0000250|UniProtKB:Q8C165};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64125;
CC         Evidence={ECO:0000250|UniProtKB:Q8C165};
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:0000250|UniProtKB:Q8C165};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64129;
CC         Evidence={ECO:0000250|UniProtKB:Q8C165};
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:0000250|UniProtKB:Q8C165};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64133;
CC         Evidence={ECO:0000250|UniProtKB:Q8C165};
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:0000250|UniProtKB:Q8C165};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64137;
CC         Evidence={ECO:0000250|UniProtKB:Q8C165};
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:0000250|UniProtKB:Q8C165};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:51318;
CC         Evidence={ECO:0000250|UniProtKB:Q8C165};
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:0000250|UniProtKB:Q8C165};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64193;
CC         Evidence={ECO:0000250|UniProtKB:Q8C165};
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:0000250|UniProtKB:Q8C165};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64145;
CC         Evidence={ECO:0000250|UniProtKB:Q8C165};
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:0000250|UniProtKB:Q8C165};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51353;
CC         Evidence={ECO:0000250|UniProtKB:Q8C165};
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:0000250|UniProtKB:Q8C165};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64177;
CC         Evidence={ECO:0000250|UniProtKB:Q8C165};
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:0000250|UniProtKB:Q8C165};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64185;
CC         Evidence={ECO:0000250|UniProtKB:Q8C165};
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:0000250|UniProtKB:Q8C165};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51357;
CC         Evidence={ECO:0000250|UniProtKB:Q8C165};
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:0000250|UniProtKB:Q8C165};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64117;
CC         Evidence={ECO:0000250|UniProtKB:Q8C165};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:64118;
CC         Evidence={ECO:0000250|UniProtKB:Q8C165};
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:0000250|UniProtKB:Q8C165};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51313;
CC         Evidence={ECO:0000250|UniProtKB:Q8C165};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:51314;
CC         Evidence={ECO:0000250|UniProtKB:Q8C165};
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:0000250|UniProtKB:Q8C165}.
CC   -!- PATHWAY: Amino-acid metabolism. {ECO:0000269|PubMed:27374330}.
CC   -!- PATHWAY: Energy metabolism. {ECO:0000269|PubMed:27374330}.
CC   -!- PATHWAY: Lipid metabolism; fatty acid metabolism.
CC       {ECO:0000269|PubMed:27374330}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q8C165}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q6GTS8-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q6GTS8-2; Sequence=VSP_031826, VSP_031827;
CC   -!- MISCELLANEOUS: Genetically increasing or decreasing the expression of
CC       PM20D1 reduces and aggravates Alzheimer's disease (AD) related
CC       pathologies, respectively. These findings suggest that in a particular
CC       genetic background, PM20D1 contributes to neuroprotection against AD.
CC       {ECO:0000269|PubMed:29736028}.
CC   -!- SIMILARITY: Belongs to the peptidase M20A family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Protein Spotlight; Note=A touch of warmth - Issue
CC       195 of September 2017;
CC       URL="https://web.expasy.org/spotlight/back_issues/195/";
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DR   EMBL; AK057131; BAB71368.1; -; mRNA.
DR   EMBL; AK290786; BAF83475.1; -; mRNA.
DR   EMBL; AC119673; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC039170; AAH39170.1; -; mRNA.
DR   EMBL; BC063477; AAH63477.1; -; mRNA.
DR   CCDS; CCDS1460.1; -. [Q6GTS8-1]
DR   RefSeq; NP_689704.4; NM_152491.4. [Q6GTS8-1]
DR   AlphaFoldDB; Q6GTS8; -.
DR   SMR; Q6GTS8; -.
DR   BioGRID; 127171; 23.
DR   IntAct; Q6GTS8; 2.
DR   STRING; 9606.ENSP00000356104; -.
DR   SwissLipids; SLP:000001665; -.
DR   MEROPS; M20.011; -.
DR   GlyCosmos; Q6GTS8; 1 site, No reported glycans.
DR   GlyGen; Q6GTS8; 3 sites.
DR   iPTMnet; Q6GTS8; -.
DR   PhosphoSitePlus; Q6GTS8; -.
DR   BioMuta; PM20D1; -.
DR   DMDM; 317373406; -.
DR   MassIVE; Q6GTS8; -.
DR   PaxDb; 9606-ENSP00000356104; -.
DR   PeptideAtlas; Q6GTS8; -.
DR   ProteomicsDB; 66320; -. [Q6GTS8-1]
DR   ProteomicsDB; 66321; -. [Q6GTS8-2]
DR   Antibodypedia; 2556; 31 antibodies from 13 providers.
DR   DNASU; 148811; -.
DR   Ensembl; ENST00000367136.5; ENSP00000356104.4; ENSG00000162877.13. [Q6GTS8-1]
DR   GeneID; 148811; -.
DR   KEGG; hsa:148811; -.
DR   MANE-Select; ENST00000367136.5; ENSP00000356104.4; NM_152491.5; NP_689704.4.
DR   UCSC; uc001hdj.4; human. [Q6GTS8-1]
DR   AGR; HGNC:26518; -.
DR   CTD; 148811; -.
DR   DisGeNET; 148811; -.
DR   GeneCards; PM20D1; -.
DR   HGNC; HGNC:26518; PM20D1.
DR   HPA; ENSG00000162877; Group enriched (pancreas, skin).
DR   MIM; 617124; gene.
DR   neXtProt; NX_Q6GTS8; -.
DR   OpenTargets; ENSG00000162877; -.
DR   PharmGKB; PA162399772; -.
DR   VEuPathDB; HostDB:ENSG00000162877; -.
DR   eggNOG; KOG2275; Eukaryota.
DR   GeneTree; ENSGT00940000156659; -.
DR   HOGENOM; CLU_021802_11_1_1; -.
DR   InParanoid; Q6GTS8; -.
DR   OMA; NYGDHSG; -.
DR   OrthoDB; 3672990at2759; -.
DR   PhylomeDB; Q6GTS8; -.
DR   TreeFam; TF328688; -.
DR   PathwayCommons; Q6GTS8; -.
DR   Reactome; R-HSA-9673163; Oleoyl-phe metabolism.
DR   SignaLink; Q6GTS8; -.
DR   UniPathway; UPA00199; -.
DR   BioGRID-ORCS; 148811; 11 hits in 1142 CRISPR screens.
DR   ChiTaRS; PM20D1; human.
DR   GenomeRNAi; 148811; -.
DR   Pharos; Q6GTS8; Tdark.
DR   PRO; PR:Q6GTS8; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   RNAct; Q6GTS8; Protein.
DR   Bgee; ENSG00000162877; Expressed in upper leg skin and 95 other cell types or tissues.
DR   Genevisible; Q6GTS8; HS.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
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; EXP:Reactome.
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; TAS:Reactome.
DR   GO; GO:0043604; P:amide biosynthetic process; IDA:UniProtKB.
DR   GO; GO:0043605; P:amide catabolic process; IDA:UniProtKB.
DR   GO; GO:0006520; P:amino acid metabolic process; IDA:UniProtKB.
DR   GO; GO:0044255; P:cellular lipid metabolic process; IDA:UniProtKB.
DR   GO; GO:0097009; P:energy homeostasis; IEA:Ensembl.
DR   GO; GO:0006631; P:fatty acid metabolic process; IEA:UniProtKB-UniPathway.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   CDD; cd05674; M20_yscS; 1.
DR   Gene3D; 1.10.150.900; -; 1.
DR   Gene3D; 3.30.70.360; -; 1.
DR   Gene3D; 3.40.630.10; Zn peptidases; 1.
DR   InterPro; IPR036264; Bact_exopeptidase_dim_dom.
DR   InterPro; IPR047177; Pept_M20A.
DR   InterPro; IPR002933; Peptidase_M20.
DR   InterPro; IPR011650; Peptidase_M20_dimer.
DR   PANTHER; PTHR45962; N-FATTY-ACYL-AMINO ACID SYNTHASE/HYDROLASE PM20D1; 1.
DR   PANTHER; PTHR45962:SF1; N-FATTY-ACYL-AMINO ACID SYNTHASE_HYDROLASE PM20D1; 1.
DR   Pfam; PF07687; M20_dimer; 1.
DR   Pfam; PF01546; Peptidase_M20; 1.
DR   SUPFAM; SSF55031; Bacterial exopeptidase dimerisation domain; 1.
DR   SUPFAM; SSF53187; Zn-dependent exopeptidases; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; Glycoprotein; Hydrolase; Lipid metabolism; Lyase;
KW   Metal-binding; Protease; Reference proteome; Secreted; Signal; Zinc.
FT   SIGNAL          1..25
FT                   /evidence="ECO:0000255"
FT   CHAIN           26..502
FT                   /note="N-fatty-acyl-amino acid synthase/hydrolase PM20D1"
FT                   /id="PRO_0000321928"
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         217
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         464
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        252
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VAR_SEQ         302..361
FT                   /note="FPFPVNIILSNPWLFEPLISRFMERNPLTNAIIRTTTALTIFKAGVKFNVIP
FT                   PVAQATVN -> VYGEKSLNQCNNQDHHGTHHIQSRGQVQCHPPSGPGHSQLPDSPWTD
FT                   SPRGPRTHEEHCG (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_031826"
FT   VAR_SEQ         362..502
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_031827"
FT   VARIANT         33
FT                   /note="H -> Y (in dbSNP:rs11540014)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_039380"
FT   VARIANT         149
FT                   /note="I -> V (in dbSNP:rs1891460)"
FT                   /evidence="ECO:0000269|PubMed:14702039,
FT                   ECO:0000269|PubMed:15489334"
FT                   /id="VAR_039381"
FT   VARIANT         153
FT                   /note="R -> W (in dbSNP:rs1104899)"
FT                   /evidence="ECO:0000269|PubMed:14702039,
FT                   ECO:0000269|PubMed:15489334"
FT                   /id="VAR_039382"
FT   VARIANT         237
FT                   /note="I -> T (in dbSNP:rs7518979)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_039383"
FT   VARIANT         258
FT                   /note="S -> C (in dbSNP:rs11581214)"
FT                   /id="VAR_039384"
FT   VARIANT         346
FT                   /note="G -> R (in dbSNP:rs11240573)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_039385"
FT   VARIANT         380
FT                   /note="I -> T (in dbSNP:rs1361754)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_039386"
FT   CONFLICT        84
FT                   /note="H -> R (in Ref. 3; AAH39170)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   502 AA;  55741 MW;  0CC2C45E1A7ADEA8 CRC64;
     MAQRCVCVLA LVAMLLLVFP TVSRSMGPRS GEHQRASRIP SQFSKEERVA MKEALKGAIQ
     IPTVTFSSEK SNTTALAEFG KYIHKVFPTV VSTSFIQHEV VEEYSHLFTI QGSDPSLQPY
     LLMAHFDVVP APEEGWEVPP FSGLERDGII YGRGTLDDKN SVMALLQALE LLLIRKYIPR
     RSFFISLGHD EESSGTGAQR ISALLQSRGV QLAFIVDEGG FILDDFIPNF KKPIALIAVS
     EKGSMNLMLQ VNMTSGHSSA PPKETSIGIL AAAVSRLEQT PMPIIFGSGT VVTVLQQLAN
     EFPFPVNIIL SNPWLFEPLI SRFMERNPLT NAIIRTTTAL TIFKAGVKFN VIPPVAQATV
     NFRIHPGQTV QEVLELTKNI VADNRVQFHV LSAFDPLPVS PSDDKALGYQ LLRQTVQSVF
     PEVNITAPVT SIGNTDSRFF TNLTTGIYRF YPIYIQPEDF KRIHGVNEKI SVQAYETQVK
     FIFELIQNAD TDQEPVSHLH KL
//