| IED ID | IndEnz0005000020 |
| Enzyme Type ID | lipase000020 |
| Protein Name |
Lysophosphatidylserine lipase ABHD12 EC 3.1.-.- 2-arachidonoylglycerol hydrolase ABHD12 Abhydrolase domain-containing protein 12 hABHD12 Monoacylglycerol lipase ABHD12 EC 3.1.1.23 Oxidized phosphatidylserine lipase ABHD12 EC 3.1.-.- |
| Gene Name | ABHD12 C20orf22 |
| Organism | Homo sapiens (Human) |
| 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 Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MRKRTEPVALEHERCAAAGSSSSGSAAAALDADCRLKQNLRLTGPAAAEPRCAADAGMKRALGRRKGVWLRLRKILFCVLGLYIAIPFLIKLCPGIQAKLIFLNFVRVPYFIDLKKPQDQGLNHTCNYYLQPEEDVTIGVWHTVPAVWWKNAQGKDQMWYEDALASSHPIILYLHGNAGTRGGDHRVELYKVLSSLGYHVVTFDYRGWGDSVGTPSERGMTYDALHVFDWIKARSGDNPVYIWGHSLGTGVATNLVRRLCERETPPDALILESPFTNIREEAKSHPFSVIYRYFPGFDWFFLDPITSSGIKFANDENVKHISCPLLILHAEDDPVVPFQLGRKLYSIAAPARSFRDFKVQFVPFHSDLGYRHKYIYKSPELPRILREFLGKSEPEHQH |
| Enzyme Length | 398 |
| Uniprot Accession Number | Q8N2K0 |
| Absorption | |
| Active Site | ACT_SITE 246; /note="Nucleophile"; /evidence="ECO:0000305|PubMed:22969151, ECO:0000305|PubMed:30237167"; ACT_SITE 333; /note="Charge relay system"; /evidence="ECO:0000305|PubMed:22969151"; ACT_SITE 372; /note="Charge relay system"; /evidence="ECO:0000305|PubMed:22969151" |
| Activity Regulation | ACTIVITY REGULATION: Selectively inhibited by DO264 (N-3-pyridyl-N'-(1-[3-chloro-4-{2-chloro-4-(trifluoromethoxy)phenoxy}pyridine-2-yl]piperidin-4-yl)thiourea) (PubMed:30420694, PubMed:30720278). Reversibly inhibited by triterpenoids, but with rather low potency (PubMed:24879289). {ECO:0000269|PubMed:24879289, ECO:0000269|PubMed:30420694, ECO:0000269|PubMed:30720278}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=1-(9Z-octadecenoyl)-sn-glycero-3-phospho-L-serine + H2O = (9Z)-octadecenoate + H(+) + sn-glycero-3-phospho-L-serine; Xref=Rhea:RHEA:40499, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:64765, ChEBI:CHEBI:74617; Evidence={ECO:0000269|PubMed:25290914, ECO:0000269|PubMed:30237167};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40500; Evidence={ECO:0000269|PubMed:25290914, ECO:0000269|PubMed:30237167}; CATALYTIC ACTIVITY: Reaction=1-(9Z-octadecenoyl)-sn-glycero-3-phospho-(1'-sn-glycerol) + H2O = (9Z)-octadecenoate + H(+) + sn-glycero-3-phospho-(1'-sn-glycerol); Xref=Rhea:RHEA:44584, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:64717, ChEBI:CHEBI:72828; Evidence={ECO:0000250|UniProtKB:Q99LR1}; CATALYTIC ACTIVITY: Reaction=1-(9Z-octadecenoyl)-sn-glycero-3-phospho-(1D-myo-inositol) + H2O = (9Z)-octadecenoate + H(+) + sn-glycero-3-phospho-1D-myo-inositol; Xref=Rhea:RHEA:44588, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:58444, ChEBI:CHEBI:78762; Evidence={ECO:0000250|UniProtKB:Q99LR1}; CATALYTIC ACTIVITY: Reaction=1-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine + H2O = (9Z)-octadecenoate + H(+) + sn-glycero-3-phosphoethanolamine; Xref=Rhea:RHEA:40895, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:74971, ChEBI:CHEBI:143890; Evidence={ECO:0000250|UniProtKB:Q99LR1}; CATALYTIC ACTIVITY: Reaction=1-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + H2O = 1-(9Z-octadecenoyl)-sn-glycerol + H(+) + phosphocholine; Xref=Rhea:RHEA:41091, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28610, ChEBI:CHEBI:75757, ChEBI:CHEBI:295975; Evidence={ECO:0000250|UniProtKB:Q99LR1}; CATALYTIC ACTIVITY: Reaction=2-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-octadecenoate + glycerol + H(+); Xref=Rhea:RHEA:38491, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:30823, ChEBI:CHEBI:73990; Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:30237167};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38492; Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:30237167}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoyl-sn-glycero-3-phospho-L-serine + H2O = H(+) + hexadecanoate + sn-glycero-3-phospho-L-serine; Xref=Rhea:RHEA:44552, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:64765, ChEBI:CHEBI:75020; Evidence={ECO:0000269|PubMed:30237167};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44553; Evidence={ECO:0000269|PubMed:30237167}; CATALYTIC ACTIVITY: Reaction=2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + glycerol + H(+); Xref=Rhea:RHEA:26132, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:32395, ChEBI:CHEBI:52392; Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:30237167};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:26133; Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:30237167}; CATALYTIC ACTIVITY: Reaction=Hydrolyzes glycerol monoesters of long-chain fatty acids.; EC=3.1.1.23; Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:30237167}; CATALYTIC ACTIVITY: Reaction=1-decanoylglycerol + H2O = decanoate + glycerol + H(+); Xref=Rhea:RHEA:44320, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:27689, ChEBI:CHEBI:75547; Evidence={ECO:0000269|PubMed:22969151};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44321; Evidence={ECO:0000269|PubMed:22969151}; CATALYTIC ACTIVITY: Reaction=1-dodecanoylglycerol + H2O = dodecanoate + glycerol + H(+); Xref=Rhea:RHEA:44316, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:18262, ChEBI:CHEBI:75539; Evidence={ECO:0000269|PubMed:22969151};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44317; Evidence={ECO:0000269|PubMed:22969151}; CATALYTIC ACTIVITY: Reaction=1-tetradecanoylglycerol + H2O = glycerol + H(+) + tetradecanoate; Xref=Rhea:RHEA:44312, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:30807, ChEBI:CHEBI:75562; Evidence={ECO:0000269|PubMed:22969151};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44313; Evidence={ECO:0000269|PubMed:22969151}; CATALYTIC ACTIVITY: Reaction=2-hexadecanoylglycerol + H2O = glycerol + H(+) + hexadecanoate; Xref=Rhea:RHEA:39963, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:75455; Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:30237167};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39964; Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:30237167}; CATALYTIC ACTIVITY: Reaction=1-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-octadecenoate + glycerol + H(+); Xref=Rhea:RHEA:38487, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:30823, ChEBI:CHEBI:75342; Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:30237167};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38488; Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:30237167}; CATALYTIC ACTIVITY: Reaction=2-(9Z,12Z-octadecadienoyl)-glycerol + H2O = (9Z,12Z)-octadecadienoate + glycerol + H(+); Xref=Rhea:RHEA:44732, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:30245, ChEBI:CHEBI:75457; Evidence={ECO:0000269|PubMed:22969151};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44733; Evidence={ECO:0000269|PubMed:22969151}; CATALYTIC ACTIVITY: Reaction=1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + glycerol + H(+); Xref=Rhea:RHEA:44728, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:32395, ChEBI:CHEBI:75612; Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:25290914, ECO:0000269|PubMed:30237167};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44729; Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:25290914, ECO:0000269|PubMed:30237167}; CATALYTIC ACTIVITY: Reaction=1-(9Z,12Z-octadecadienoyl)-glycerol + H2O = (9Z,12Z)-octadecadienoate + glycerol + H(+); Xref=Rhea:RHEA:48428, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:30245, ChEBI:CHEBI:75568; Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:25290914};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48429; Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:25290914}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoylglycerol + H2O = glycerol + H(+) + hexadecanoate; Xref=Rhea:RHEA:39959, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:69081; Evidence={ECO:0000269|PubMed:30237167};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39960; Evidence={ECO:0000269|PubMed:30237167}; CATALYTIC ACTIVITY: Reaction=1-octadecanoylglycerol + H2O = glycerol + H(+) + octadecanoate; Xref=Rhea:RHEA:38363, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:25629, ChEBI:CHEBI:75555; Evidence={ECO:0000269|PubMed:30237167};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38364; Evidence={ECO:0000269|PubMed:30237167}; CATALYTIC ACTIVITY: Reaction=1-octadecanoyl-2-(9,10-epoxyoctadecanoyl)-sn-glycero-3-phospho-L-serine + H2O = 1-octadecanoyl-sn-glycero-3-phosphoserine + 9,10-epoxyoctadecanoate + H(+); Xref=Rhea:RHEA:59364, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:84467, ChEBI:CHEBI:85195, ChEBI:CHEBI:143087; Evidence={ECO:0000269|PubMed:30643283};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59365; Evidence={ECO:0000269|PubMed:30643283}; CATALYTIC ACTIVITY: Reaction=1-octadecanoyl-2-(10-hydroxyoctadecanoyl)-sn-glycero-3-phospho-L-serine + H2O = 1-octadecanoyl-sn-glycero-3-phosphoserine + 10-hydroxyoctadecanoate + H(+); Xref=Rhea:RHEA:59368, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:84467, ChEBI:CHEBI:143088, ChEBI:CHEBI:143089; Evidence={ECO:0000269|PubMed:30643283};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59369; Evidence={ECO:0000269|PubMed:30643283}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoyl-2-(10-hydroxyoctadecanoyl)-sn-glycero-3-phospho-L-serine + H2O = 1-hexadecanoyl-sn-glycero-3-phospho-L-serine + 10-hydroxyoctadecanoate + H(+); Xref=Rhea:RHEA:59372, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:75020, ChEBI:CHEBI:143089, ChEBI:CHEBI:143094; Evidence={ECO:0000269|PubMed:30643283};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59373; Evidence={ECO:0000269|PubMed:30643283}; |
| DNA Binding | |
| EC Number | 3.1.-.-; 3.1.1.23 |
| Enzyme Function | FUNCTION: Lysophosphatidylserine (LPS) lipase that mediates the hydrolysis of lysophosphatidylserine, a class of signaling lipids that regulates immunological and neurological processes (PubMed:25290914, PubMed:30237167, PubMed:30420694, PubMed:30720278, PubMed:30643283). Represents a major lysophosphatidylserine lipase in the brain, thereby playing a key role in the central nervous system (By similarity). Also able to hydrolyze oxidized phosphatidylserine; oxidized phosphatidylserine is produced in response to severe inflammatory stress and constitutes a proapoptotic 'eat me' signal (PubMed:30643283). Also has monoacylglycerol (MAG) lipase activity: hydrolyzes 2-arachidonoylglycerol (2-AG), thereby acting as a regulator of endocannabinoid signaling pathways (PubMed:22969151, PubMed:24027063). Has a strong preference for very-long-chain lipid substrates; substrate specificity is likely due to improved catalysis and not improved substrate binding (PubMed:30237167). {ECO:0000250|UniProtKB:Q99LR1, ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:24027063, ECO:0000269|PubMed:25290914, ECO:0000269|PubMed:30237167, ECO:0000269|PubMed:30420694, ECO:0000269|PubMed:30643283, ECO:0000269|PubMed:30720278}. |
| Temperature Dependency | |
| PH Dependency | BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 7.2-9 with 2-arachidonoyglycerol as substrate. {ECO:0000269|PubMed:22969151}; |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (3); Alternative sequence (2); Chain (1); Glycosylation (1); Mutagenesis (3); Natural variant (9); Sequence conflict (2); Topological domain (2); Transmembrane (1) |
| Keywords | Alternative splicing;Cataract;Deafness;Disease variant;Endoplasmic reticulum;Glycoprotein;Hydrolase;Lipid metabolism;Membrane;Neuropathy;Reference proteome;Retinitis pigmentosa;Transmembrane;Transmembrane helix |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000269|PubMed:30237167}; Single-pass membrane protein {ECO:0000255}. |
| Modified Residue | |
| Post Translational Modification | PTM: Glycosylated; glycosylation is required for optimal activity. {ECO:0000269|PubMed:30237167}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 21418147; 21911578; 23490117; 26638075; 28448692; 30974196; 32366405; 32462874; |
| Motif | |
| Gene Encoded By | |
| Mass | 45,097 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=117 uM for 2-arachidonoyglycerol {ECO:0000269|PubMed:22969151}; Vmax=42 nmol/min/mg enzyme toward 2-arachidonoyglycerol {ECO:0000269|PubMed:22969151}; |
| Metal Binding | |
| Rhea ID | RHEA:40499; RHEA:40500; RHEA:44584; RHEA:44588; RHEA:40895; RHEA:41091; RHEA:38491; RHEA:38492; RHEA:44552; RHEA:44553; RHEA:26132; RHEA:26133; RHEA:44320; RHEA:44321; RHEA:44316; RHEA:44317; RHEA:44312; RHEA:44313; RHEA:39963; RHEA:39964; RHEA:38487; RHEA:38488; RHEA:44732; RHEA:44733; RHEA:44728; RHEA:44729; RHEA:48428; RHEA:48429; RHEA:39959; RHEA:39960; RHEA:38363; RHEA:38364; RHEA:59364; RHEA:59365; RHEA:59368; RHEA:59369; RHEA:59372; RHEA:59373 |
| Cross Reference Brenda |