| IED ID | IndEnz0002007343 |
| Enzyme Type ID | protease007343 |
| Protein Name |
N-fatty-acyl-amino acid synthase/hydrolase PM20D1 EC 3.5.1.114 EC 3.5.1.14 Peptidase M20 domain-containing protein 1 PM20D1 |
| Gene Name | Pm20d1 |
| Organism | Mus musculus (Mouse) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Mus Mus Mus musculus (Mouse) |
| Enzyme Sequence | MAELLASLPAWAAVLLLFFATVSGSTGPRSRENRGASRIPSQFSEEERVAIKEALKGAIQIPTVSFSHEESNTTALAEFGEYIRKAFPTVFHSSLVQHEVVAKYSHLFTIQGSDPSLQPYMLMAHIDVVPAPEEGWEVPPFSGLERNGFIYGRGALDNKNSVMAILHALELLLIRNYSPKRSFFIALGHDEEVSGEKGAQKISALLQARGVQLAFLVDEGSFILEGFIPNLEKPVAMISVTEKGALDLMLQVNMTPGHSSAPPKETSIGILSAAVSRLEQTPMPNMFGGGPLKKTMKLLANEFSFPINIVLRNLWLFHPIVSRIMERNPITNALVRTTTALTMFNAGIKVNVIPPLAQATINCRIHPSQTVHEVLELVKNTVADDRVQLHVLRSFEPLPISPSDDQAMGYQLLQETIRSVFPEVDIVVPGICIANTDTRHYANITNGMYRFNPLPLNPQDFSGVHGINEKVSVQNYQNQVKFIFEFIQNADTYKEPVPHLHEL |
| Enzyme Length | 503 |
| Uniprot Accession Number | Q8C165 |
| Absorption | |
| Active Site | ACT_SITE 127; /evidence=ECO:0000250; ACT_SITE 191; /note=Proton acceptor; /evidence=ECO:0000250 |
| Activity Regulation | ACTIVITY REGULATION: Lipoproteins are powerful coactivators of PM20D1 activity in vitro and NAA biosynthesis in vivo. {ECO:0000269|PubMed:32402239}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=an N-acyl-L-amino acid + H2O = a carboxylate + an L-alpha-amino acid; Xref=Rhea:RHEA:15565, ChEBI:CHEBI:15377, ChEBI:CHEBI:29067, ChEBI:CHEBI:59869, ChEBI:CHEBI:59874; EC=3.5.1.14; Evidence={ECO:0000269|PubMed:27374330, ECO:0000269|PubMed:29967167, ECO:0000269|PubMed:32271712, ECO:0000269|PubMed:32402239};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15566; Evidence={ECO:0000269|PubMed:27374330, ECO:0000269|PubMed:29967167, ECO:0000269|PubMed:32271712, ECO:0000269|PubMed:32402239};PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:15567; Evidence={ECO:0000269|PubMed:27374330, ECO:0000269|PubMed:32271712}; CATALYTIC ACTIVITY: Reaction=an N-acyl-aromatic L-alpha-amino acid + H2O = a carboxylate + an aromatic L-alpha-amino acid; Xref=Rhea:RHEA:54184, ChEBI:CHEBI:15377, ChEBI:CHEBI:29067, ChEBI:CHEBI:84824, ChEBI:CHEBI:138093; EC=3.5.1.114; Evidence={ECO:0000269|PubMed:27374330, ECO:0000269|PubMed:29533650, ECO:0000269|PubMed:29967167, ECO:0000269|PubMed:32271712, ECO:0000269|PubMed:32402239};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54185; Evidence={ECO:0000269|PubMed:27374330, ECO:0000269|PubMed:29533650, ECO:0000269|PubMed:29967167, ECO:0000269|PubMed:32271712};PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:54186; Evidence={ECO:0000269|PubMed:27374330, ECO:0000269|PubMed:29967167, ECO:0000269|PubMed:32271712, ECO:0000269|PubMed:32402239}; CATALYTIC ACTIVITY: Reaction=H2O + N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-glycine = (5Z,8Z,11Z,14Z)-eicosatetraenoate + glycine; Xref=Rhea:RHEA:64108, ChEBI:CHEBI:15377, ChEBI:CHEBI:32395, ChEBI:CHEBI:57305, ChEBI:CHEBI:59002; Evidence={ECO:0000269|PubMed:29967167, ECO:0000269|PubMed:32271712, ECO:0000269|PubMed:32402239};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64109; Evidence={ECO:0000269|PubMed:29967167, ECO:0000269|PubMed:32271712, ECO:0000269|PubMed:32402239};PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:64110; Evidence={ECO:0000269|PubMed:32271712}; CATALYTIC ACTIVITY: Reaction=H2O + N-hexadecanoyl-L-phenylalanine = hexadecanoate + L-phenylalanine; Xref=Rhea:RHEA:64124, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, ChEBI:CHEBI:58095, ChEBI:CHEBI:149699; Evidence={ECO:0000269|PubMed:32271712};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64125; Evidence={ECO:0000269|PubMed:32271712}; CATALYTIC ACTIVITY: Reaction=H2O + N-octadecanoyl-L-phenylalanine = L-phenylalanine + octadecanoate; Xref=Rhea:RHEA:64128, ChEBI:CHEBI:15377, ChEBI:CHEBI:25629, ChEBI:CHEBI:58095, ChEBI:CHEBI:149700; Evidence={ECO:0000269|PubMed:32271712};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64129; Evidence={ECO:0000269|PubMed:32271712}; CATALYTIC ACTIVITY: Reaction=H2O + N-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-L-phenylalanine = (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + L-phenylalanine; Xref=Rhea:RHEA:64132, ChEBI:CHEBI:15377, ChEBI:CHEBI:58095, ChEBI:CHEBI:77016, ChEBI:CHEBI:149701; Evidence={ECO:0000269|PubMed:32271712};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64133; Evidence={ECO:0000269|PubMed:32271712}; CATALYTIC ACTIVITY: Reaction=H2O + N-(9Z-octadecenoyl)-L-asparagine = (9Z)-octadecenoate + L-asparagine; Xref=Rhea:RHEA:64136, ChEBI:CHEBI:15377, ChEBI:CHEBI:30823, ChEBI:CHEBI:58048, ChEBI:CHEBI:149730; Evidence={ECO:0000269|PubMed:32271712};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64137; Evidence={ECO:0000269|PubMed:32271712}; CATALYTIC ACTIVITY: Reaction=(9Z)-octadecenoate + glycine = H2O + N-(9Z-octadecenoyl)glycine; Xref=Rhea:RHEA:51316, ChEBI:CHEBI:15377, ChEBI:CHEBI:30823, ChEBI:CHEBI:57305, ChEBI:CHEBI:133992; Evidence={ECO:0000269|PubMed:27374330, ECO:0000269|PubMed:32271712};PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:51318; Evidence={ECO:0000269|PubMed:27374330, ECO:0000269|PubMed:32271712}; CATALYTIC ACTIVITY: Reaction=H2O + N-(9Z-octadecenoyl)-L-lysine = (9Z)-octadecenoate + L-lysine; Xref=Rhea:RHEA:64192, ChEBI:CHEBI:15377, ChEBI:CHEBI:30823, ChEBI:CHEBI:32551, ChEBI:CHEBI:149731; Evidence={ECO:0000269|PubMed:32271712};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64193; Evidence={ECO:0000269|PubMed:32271712}; CATALYTIC ACTIVITY: Reaction=H2O + N-(9Z-octadecenoyl)-L-methionine = (9Z)-octadecenoate + L-methionine; Xref=Rhea:RHEA:64144, ChEBI:CHEBI:15377, ChEBI:CHEBI:30823, ChEBI:CHEBI:57844, ChEBI:CHEBI:149732; Evidence={ECO:0000269|PubMed:32271712};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64145; Evidence={ECO:0000269|PubMed:32271712}; CATALYTIC ACTIVITY: Reaction=H2O + N-(9Z-octadecenoyl)-L-serine = (9Z)-octadecenoate + L-serine; Xref=Rhea:RHEA:51352, ChEBI:CHEBI:15377, ChEBI:CHEBI:30823, ChEBI:CHEBI:33384, ChEBI:CHEBI:134031; Evidence={ECO:0000269|PubMed:27374330, ECO:0000269|PubMed:32271712};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51353; Evidence={ECO:0000269|PubMed:27374330, ECO:0000269|PubMed:32271712}; CATALYTIC ACTIVITY: Reaction=H2O + N-(9Z-octadecenoyl)-L-tryptophan = (9Z)-octadecenoate + L-tryptophan; Xref=Rhea:RHEA:64176, ChEBI:CHEBI:15377, ChEBI:CHEBI:30823, ChEBI:CHEBI:57912, ChEBI:CHEBI:149733; Evidence={ECO:0000269|PubMed:32271712};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64177; Evidence={ECO:0000269|PubMed:32271712}; CATALYTIC ACTIVITY: Reaction=H2O + N-(9Z-octadecenoyl)-L-tyrosine = (9Z)-octadecenoate + L-tyrosine; Xref=Rhea:RHEA:64184, ChEBI:CHEBI:15377, ChEBI:CHEBI:30823, ChEBI:CHEBI:58315, ChEBI:CHEBI:149734; Evidence={ECO:0000269|PubMed:32271712};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64185; Evidence={ECO:0000269|PubMed:32271712}; CATALYTIC ACTIVITY: Reaction=H2O + N-(9Z-octadecenoyl)-L-glutamine = (9Z)-octadecenoate + L-glutamine; Xref=Rhea:RHEA:51356, ChEBI:CHEBI:15377, ChEBI:CHEBI:30823, ChEBI:CHEBI:58359, ChEBI:CHEBI:134033; Evidence={ECO:0000269|PubMed:27374330, ECO:0000269|PubMed:32271712};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51357; Evidence={ECO:0000269|PubMed:27374330, ECO:0000269|PubMed:32271712}; CATALYTIC ACTIVITY: Reaction=H2O + N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-L-serine = (5Z,8Z,11Z,14Z)-eicosatetraenoate + L-serine; Xref=Rhea:RHEA:64116, ChEBI:CHEBI:15377, ChEBI:CHEBI:32395, ChEBI:CHEBI:33384, ChEBI:CHEBI:149697; Evidence={ECO:0000269|PubMed:32271712};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64117; Evidence={ECO:0000269|PubMed:32271712};PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:64118; Evidence={ECO:0000269|PubMed:32271712}; CATALYTIC ACTIVITY: Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + L-phenylalanine = H2O + N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-L-phenylalanine; Xref=Rhea:RHEA:51312, ChEBI:CHEBI:15377, ChEBI:CHEBI:32395, ChEBI:CHEBI:58095, ChEBI:CHEBI:134022; Evidence={ECO:0000269|PubMed:32271712};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51313; Evidence={ECO:0000269|PubMed:32271712};PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:51314; Evidence={ECO:0000269|PubMed:32271712}; CATALYTIC ACTIVITY: Reaction=H2O + N-(9Z-octadecenoyl)-L-leucine = (9Z)-octadecenoate + L-leucine; Xref=Rhea:RHEA:51360, ChEBI:CHEBI:15377, ChEBI:CHEBI:30823, ChEBI:CHEBI:57427, ChEBI:CHEBI:134035; Evidence={ECO:0000269|PubMed:27374330};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51361; Evidence={ECO:0000269|PubMed:27374330};PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:51362; Evidence={ECO:0000269|PubMed:27374330}; CATALYTIC ACTIVITY: Reaction=(9Z)-octadecenoate + L-phenylalanine = H2O + N-(9Z-octadecenoyl)-L-phenylalanine; Xref=Rhea:RHEA:51300, ChEBI:CHEBI:15377, ChEBI:CHEBI:30823, ChEBI:CHEBI:58095, ChEBI:CHEBI:134020; Evidence={ECO:0000269|PubMed:27374330, ECO:0000269|PubMed:29533650, ECO:0000269|PubMed:29967167, ECO:0000269|PubMed:32402239};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51301; Evidence={ECO:0000269|PubMed:27374330, ECO:0000269|PubMed:29967167, ECO:0000269|PubMed:32402239};PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:51302; Evidence={ECO:0000269|PubMed:27374330, ECO:0000269|PubMed:29533650, ECO:0000269|PubMed:29967167}; |
| DNA Binding | |
| EC Number | 3.5.1.114; 3.5.1.14 |
| Enzyme Function | FUNCTION: Secreted enzyme that regulates the endogenous N-fatty acyl amino acid (NAAs) tissue and circulating levels by functioning as a bidirectional NAA synthase/hydrolase. It condenses free fatty acids and free amino acids to generate NAAs and bidirectionally catalyzes the reverse hydrolysis reaction (PubMed:27374330, PubMed:29533650, PubMed:29967167, PubMed:32271712, PubMed:32402239) (Probable). Some of these NAAs stimulate oxidative metabolism via mitochondrial uncoupling, increasing energy expenditure in a UPC1-independent manner. Thereby, this secreted protein may indirectly regulate whole body energy expenditure (PubMed:27374330, PubMed:29967167, PubMed:32271712). PM20D1 circulates in tight association with both low- and high-density (LDL and HDL,respectively) lipoprotein particles (PubMed:32402239). {ECO:0000269|PubMed:27374330, ECO:0000269|PubMed:29533650, ECO:0000269|PubMed:29967167, ECO:0000269|PubMed:32271712, ECO:0000269|PubMed:32402239, ECO:0000305|PubMed:31659023}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | PATHWAY: Amino-acid metabolism. {ECO:0000269|PubMed:27374330, ECO:0000269|PubMed:29967167, ECO:0000269|PubMed:32271712, ECO:0000269|PubMed:32402239}.; PATHWAY: Energy metabolism; electron transfer. {ECO:0000269|PubMed:27374330, ECO:0000269|PubMed:29967167, ECO:0000269|PubMed:32271712}.; PATHWAY: Lipid metabolism; fatty acid metabolism. {ECO:0000269|PubMed:27374330, ECO:0000269|PubMed:29967167, ECO:0000269|PubMed:32271712, ECO:0000269|PubMed:32402239}. |
| nucleotide Binding | |
| Features | Active site (2); Chain (1); Glycosylation (2); Metal binding (6); Mutagenesis (3); Sequence conflict (1); Signal peptide (1) |
| Keywords | Glycoprotein;Hydrolase;Lipid metabolism;Lyase;Metal-binding;Protease;Reference proteome;Secreted;Signal;Zinc |
| Interact With | |
| Induction | INDUCTION: Up-regulated in adipose tissue upon cold exposure. {ECO:0000269|PubMed:27374330, ECO:0000269|PubMed:31659023}. |
| Subcellular Location | SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:27374330, ECO:0000269|PubMed:32271712, ECO:0000269|PubMed:32402239}. |
| Modified Residue | |
| Post Translational Modification | |
| Signal Peptide | SIGNAL 1..24; /evidence=ECO:0000255 |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 12466851; 16615898; 21068253; 21267068; 22008794; 31568785; 33490088; 34673451; |
| Motif | |
| Gene Encoded By | |
| Mass | 55,663 |
| Kinetics | |
| Metal Binding | METAL 125; /note=Zinc 2; /evidence=ECO:0000250; METAL 157; /note=Zinc 1; /evidence=ECO:0000250; METAL 157; /note=Zinc 2; /evidence=ECO:0000250; METAL 192; /note=Zinc 1; /evidence=ECO:0000250; METAL 218; /note=Zinc 2; /evidence=ECO:0000250; METAL 465; /note=Zinc 1; /evidence=ECO:0000250 |
| Rhea ID | RHEA:15565; RHEA:15566; RHEA:15567; RHEA:54184; RHEA:54185; RHEA:54186; RHEA:64108; RHEA:64109; RHEA:64110; RHEA:64124; RHEA:64125; RHEA:64128; RHEA:64129; RHEA:64132; RHEA:64133; RHEA:64136; RHEA:64137; RHEA:51316; RHEA:51318; RHEA:64192; RHEA:64193; RHEA:64144; RHEA:64145; RHEA:51352; RHEA:51353; RHEA:64176; RHEA:64177; RHEA:64184; RHEA:64185; RHEA:51356; RHEA:51357; RHEA:64116; RHEA:64117; RHEA:64118; RHEA:51312; RHEA:51313; RHEA:51314; RHEA:51360; RHEA:51361; RHEA:51362; RHEA:51300; RHEA:51301; RHEA:51302 |
| Cross Reference Brenda |