UniProt functional annotation for P54317

UniProt code: P54317.

Organism: Homo sapiens (Human).
Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
 
Function: Lipase that primarily hydrolyzes triglycerides and galactosylglycerides (PubMed:15287741, PubMed:17401110, PubMed:19451396, PubMed:21865348, PubMed:20083229, PubMed:26494624, PubMed:18702514). In neonates, may play a major role in pancreatic digestion of dietary fats such as milk fat globules enriched in long- chain triglycerides (PubMed:23732775, PubMed:19824014, PubMed:21652702). Hydrolyzes short- medium- and long-chain fatty acyls in triglycerides without apparent positional specificity (PubMed:15287741, PubMed:17401110, PubMed:21865348, PubMed:21652702, PubMed:18702514). Can completely deacylates triacylglycerols (PubMed:21865348). When liver matures and bile salt synthesis increases, it likely functions mainly as a galactolipase and monoacylglycerol lipase. Hydrolyzes monogalactosyldiglycerols (MGDG) and digalactosyldiacylglycerols (DGDG) present in plant-based diet releasing long-chain polyunsaturated fatty acids (PubMed:15287741, PubMed:17401110, PubMed:20083229, PubMed:26494624, PubMed:18702514). Hydrolyzes medium- and long-chain fatty acyls in galactolipids (PubMed:20083229, PubMed:18702514). May act together with LIPF to hydrolyze partially digested triglycerides (PubMed:23732775). Hydrolyzes long-chain monoglycerides with high efficiency (PubMed:17401110, PubMed:21652702, PubMed:23732775). In cytotoxic T cells, contributes to perforin-dependent cell lysis, but is unlikely to mediate direct cytotoxicity (By similarity). Has also low phospholipase activity, but its physiological relevance is not clear (PubMed:17401110, PubMed:18702514). {ECO:0000250|UniProtKB:P17892, ECO:0000269|PubMed:15287741, ECO:0000269|PubMed:17401110, ECO:0000269|PubMed:18702514, ECO:0000269|PubMed:19451396, ECO:0000269|PubMed:19824014, ECO:0000269|PubMed:20083229, ECO:0000269|PubMed:21652702, ECO:0000269|PubMed:21865348, ECO:0000269|PubMed:23732775, ECO:0000269|PubMed:26494624}.
 
Catalytic activity: Reaction=a triacylglycerol + H2O = a diacylglycerol + a fatty acid + H(+); Xref=Rhea:RHEA:12044, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17855, ChEBI:CHEBI:18035, ChEBI:CHEBI:28868; EC=3.1.1.3; Evidence={ECO:0000269|PubMed:15287741, ECO:0000269|PubMed:17401110, ECO:0000269|PubMed:18702514, ECO:0000269|PubMed:19451396, ECO:0000269|PubMed:21652702, ECO:0000269|PubMed:21865348, ECO:0000269|PubMed:26494624}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12045; Evidence={ECO:0000305|PubMed:15287741, ECO:0000305|PubMed:17401110, ECO:0000305|PubMed:18702514, ECO:0000305|PubMed:19451396, ECO:0000305|PubMed:21652702, ECO:0000305|PubMed:21865348, ECO:0000305|PubMed:26494624};
Catalytic activity: Reaction=a 1,2-diacyl-3-O-(beta-D-galactosyl)-sn-glycerol + 2 H2O = 3- beta-D-galactosyl-sn-glycerol + 2 a fatty acid + 2 H(+); Xref=Rhea:RHEA:13189, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15754, ChEBI:CHEBI:17615, ChEBI:CHEBI:28868; EC=3.1.1.26; Evidence={ECO:0000269|PubMed:15287741, ECO:0000269|PubMed:17401110, ECO:0000269|PubMed:18702514, ECO:0000269|PubMed:20083229}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13190; Evidence={ECO:0000305|PubMed:15287741, ECO:0000305|PubMed:17401110, ECO:0000305|PubMed:18702514, ECO:0000305|PubMed:20083229};
Catalytic activity: Reaction=1,2,3-tri-(9Z-octadecenoyl)-glycerol + H2O = (9Z)- octadecenoate + di-(9Z)-octadecenoylglycerol + H(+); Xref=Rhea:RHEA:38575, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:53753, ChEBI:CHEBI:75945; Evidence={ECO:0000269|PubMed:18702514, ECO:0000269|PubMed:19451396, ECO:0000269|PubMed:21652702, ECO:0000269|PubMed:21865348, ECO:0000269|PubMed:26494624}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38576; Evidence={ECO:0000305|PubMed:18702514, ECO:0000305|PubMed:19451396, ECO:0000305|PubMed:21652702, ECO:0000305|PubMed:21865348, ECO:0000305|PubMed:26494624};
Catalytic activity: Reaction=di-(9Z)-octadecenoylglycerol + H2O = (9Z)-octadecenoate + (9Z- octadecenoyl)-glycerol + H(+); Xref=Rhea:RHEA:47868, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:75937, ChEBI:CHEBI:75945; Evidence={ECO:0000269|PubMed:21865348}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47869; Evidence={ECO:0000305|PubMed:21865348};
Catalytic activity: Reaction=(9Z-octadecenoyl)-glycerol + H2O = (9Z)-octadecenoate + glycerol + H(+); Xref=Rhea:RHEA:39955, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:30823, ChEBI:CHEBI:75937; Evidence={ECO:0000269|PubMed:18702514, ECO:0000269|PubMed:21865348}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39956; Evidence={ECO:0000305|PubMed:18702514, ECO:0000305|PubMed:21865348};
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:17401110, ECO:0000269|PubMed:18702514}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38488; Evidence={ECO:0000305|PubMed:17401110, ECO:0000305|PubMed:18702514};
Catalytic activity: Reaction=1,2,3-tripropanoylglycerol + H2O = dipropanoylglycerol + H(+) + propanoate; Xref=Rhea:RHEA:48024, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17272, ChEBI:CHEBI:88153, ChEBI:CHEBI:88155; Evidence={ECO:0000269|PubMed:18702514}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48025; Evidence={ECO:0000305|PubMed:18702514};
Catalytic activity: Reaction=1,2,3-tributanoylglycerol + H2O = butanoate + dibutanoylglycerol + H(+); Xref=Rhea:RHEA:40475, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17968, ChEBI:CHEBI:35020, ChEBI:CHEBI:76478; Evidence={ECO:0000269|PubMed:15287741, ECO:0000269|PubMed:17401110, ECO:0000269|PubMed:18702514, ECO:0000269|PubMed:21652702, ECO:0000269|PubMed:26494624}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40476; Evidence={ECO:0000305|PubMed:15287741, ECO:0000305|PubMed:17401110, ECO:0000305|PubMed:18702514, ECO:0000305|PubMed:21652702, ECO:0000305|PubMed:26494624};
Catalytic activity: Reaction=1,2,3-trioctanoylglycerol + H2O = dioctanoylglycerol + H(+) + octanoate; Xref=Rhea:RHEA:47864, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:25646, ChEBI:CHEBI:76978, ChEBI:CHEBI:88066; Evidence={ECO:0000269|PubMed:15287741, ECO:0000269|PubMed:17401110, ECO:0000269|PubMed:18702514, ECO:0000269|PubMed:21652702, ECO:0000269|PubMed:26494624}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47865; Evidence={ECO:0000305|PubMed:15287741, ECO:0000305|PubMed:17401110, ECO:0000305|PubMed:18702514, ECO:0000305|PubMed:21652702, ECO:0000305|PubMed:26494624};
Catalytic activity: Reaction=1,2-didecanoylglycerol + H2O = decanoate + decanoylglycerol + H(+); Xref=Rhea:RHEA:48596, ChEBI:CHEBI:11152, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:27689, ChEBI:CHEBI:90605; Evidence={ECO:0000269|PubMed:15287741}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48597; Evidence={ECO:0000305|PubMed:15287741};
Catalytic activity: Reaction=H2O + long chain 1,2-diacyl-3-O-beta-D-galactosyl-sn-glycerol = a fatty acid + H(+) + long chain acyl-3-O-beta-D-galactosyl-sn- glycerol; Xref=Rhea:RHEA:48700, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28868, ChEBI:CHEBI:90477, ChEBI:CHEBI:90770; Evidence={ECO:0000305|PubMed:18702514}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48701; Evidence={ECO:0000305|PubMed:18702514};
Catalytic activity: Reaction=1,2-dioctanoyl-3-O-beta-D-galactosyl-sn-glycerol + H2O = H(+) + octanoate + octanoyl-3-(beta-D-galactosyl)-sn-glycerol; Xref=Rhea:RHEA:48696, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:25646, ChEBI:CHEBI:90453, ChEBI:CHEBI:90769; Evidence={ECO:0000269|PubMed:20083229}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48697; Evidence={ECO:0000305|PubMed:20083229};
Catalytic activity: Reaction=1,2-didodecanoyl-3-beta-D-galactosyl-sn-glycerol + H2O = dodecanoate + dodecanoyl-3-beta-D-galactosyl-sn-glycerol + H(+); Xref=Rhea:RHEA:48540, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:18262, ChEBI:CHEBI:90340, ChEBI:CHEBI:90515; Evidence={ECO:0000269|PubMed:15287741, ECO:0000269|PubMed:17401110, ECO:0000269|PubMed:18702514}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48541; Evidence={ECO:0000305|PubMed:15287741, ECO:0000305|PubMed:17401110, ECO:0000305|PubMed:18702514};
Catalytic activity: Reaction=1-beta-D-galactosyl-2,3-didodecanoyl-sn-glycerol + H2O = 1- beta-D-galactosyl-dodecanoyl-sn-glycerol + dodecanoate + H(+); Xref=Rhea:RHEA:48536, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:18262, ChEBI:CHEBI:90342, ChEBI:CHEBI:90514; Evidence={ECO:0000269|PubMed:17401110}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48537; Evidence={ECO:0000305|PubMed:17401110};
Catalytic activity: Reaction=1,2-diacyl-3-O-[alpha-D-galactosyl-(1->6)-beta-D-galactosyl]- sn-glycerol + H2O = a fatty acid + acyl-3-O-[alpha-D-galactosyl- (1->6)-beta-D-galactosyl]-sn-glycerol + H(+); Xref=Rhea:RHEA:48372, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28396, ChEBI:CHEBI:28868, ChEBI:CHEBI:90310; Evidence={ECO:0000269|PubMed:26494624}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48373; Evidence={ECO:0000305|PubMed:26494624};
Catalytic activity: Reaction=H2O + long chain 1,2-diacyl-3-O-[alpha-D-galactosyl-(1->6)- beta-D-galactosyl]-sn-glycerol = a fatty acid + H(+) + long chain acyl-3-O-[alpha-D-galactosyl-(1->6)-beta-D-galactosyl]-sn-glycerol; Xref=Rhea:RHEA:48708, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28868, ChEBI:CHEBI:90463, ChEBI:CHEBI:90774; Evidence={ECO:0000269|PubMed:20083229}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48709; Evidence={ECO:0000305|PubMed:20083229};
Catalytic activity: Reaction=1,2-dioctanoyl-3-O-[alpha-D-galactosyl-(1->6)-beta-D- galactosyl]-sn-glycerol + H2O = H(+) + octanoate + octanoyl-3-O- [alpha-D-galactosyl-(1->6)-beta-D-galactosyl]-sn-glycerol; Xref=Rhea:RHEA:48692, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:25646, ChEBI:CHEBI:90457, ChEBI:CHEBI:90768; Evidence={ECO:0000269|PubMed:20083229}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48693; Evidence={ECO:0000305|PubMed:20083229};
Catalytic activity: Reaction=1,2-didodecanoyl-3-O-[alpha-D-galactosyl-(1->6)-beta-D- galactosyl]-sn-glycerol + H2O = dodecanoate + dodecanoyl-3-O-[alpha- D-galactosyl-(1->6)-beta-D-galactosyl]-sn-glycerol + H(+); Xref=Rhea:RHEA:48516, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:18262, ChEBI:CHEBI:90337, ChEBI:CHEBI:90359; Evidence={ECO:0000269|PubMed:17401110, ECO:0000269|PubMed:18702514}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48517; Evidence={ECO:0000305|PubMed:17401110, ECO:0000305|PubMed:18702514};
Catalytic activity: Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a fatty acid + a monoacyl-sn-glycero-3-phosphocholine + H(+); Xref=Rhea:RHEA:44664, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28868, ChEBI:CHEBI:57643, ChEBI:CHEBI:84465; Evidence={ECO:0000269|PubMed:17401110, ECO:0000269|PubMed:18702514}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44665; Evidence={ECO:0000305|PubMed:17401110, ECO:0000305|PubMed:18702514};
Activity regulation: Regulated by CLPS and bile salts levels ranging 1- 5 mM in neonates and 2-30 mM in healthy adults. CLPS stimulates milk fat digestion in the presence of 4 mM bile salts (PubMed:23732775). Triacylglycerol lipase activity toward short- and medium-chain triglycerides is inhibited by increasing concentrations of bile salts and weakly reactivated by CLPS (PubMed:15287741, PubMed:17401110, PubMed:21652702, PubMed:26494624). Optimal triacylglycerol lipase activity is reached at bile salts concentrations ranging from 0.1 to 0.5 mM and then decreases at concentrations higher than 1 mM (PubMed:21652702, PubMed:15287741, PubMed:17401110). Lipase activity toward long-chain glycerolipids is stimulated by CLPS in the presence of 4 mM bile salts (PubMed:21652702). Galactolipase activity is inhibited at high concentrations of bile salts (PubMed:20083229). Triacylglycerol lipase activity is inhibited by anti-obesity drug tetrahydrolipstatin (PubMed:17401110). {ECO:0000269|PubMed:15287741, ECO:0000269|PubMed:17401110, ECO:0000269|PubMed:20083229, ECO:0000269|PubMed:21652702, ECO:0000269|PubMed:23732775, ECO:0000269|PubMed:26494624}.
Biophysicochemical properties: pH dependence: Optimum pH is 8.8 for triacylglycerol lipase activity, 8.5 for phospholipase activity and 8 for galactolipase activity. The enzyme activities decrease in the pH 5-7 range corresponding to the physiological conditions occurring in the small intestine. {ECO:0000269|PubMed:17401110};
Pathway: Glycerolipid metabolism; triacylglycerol degradation. {ECO:0000269|PubMed:21865348}.
Pathway: Glycolipid metabolism. {ECO:0000269|PubMed:20083229}.
Subcellular location: Secreted {ECO:0000269|PubMed:18702514, ECO:0000269|PubMed:19824014}. Zymogen granule membrane {ECO:0000250|UniProtKB:P54318}; Peripheral membrane protein {ECO:0000250|UniProtKB:P54318}.
Tissue specificity: Pancreas. {ECO:0000269|PubMed:10674344}.
Developmental stage: Expressed by 16 weeks in fetal pancreas. {ECO:0000269|PubMed:10674344}.
Similarity: Belongs to the AB hydrolase superfamily. Lipase family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.