IED Industry Enzyme Database

Detail Information for IndEnz0005000623
IED ID IndEnz0005000623
Enzyme Type ID lipase000623
Protein Name Acyl-protein thioesterase 1
APT-1
hAPT1
EC 3.1.2.-
Lysophospholipase 1
Lysophospholipase I
LPL-I
LysoPLA I
Palmitoyl-protein hydrolase
EC 3.1.2.22
Gene Name LYPLA1 APT1 LPL1
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 MCGNNMSTPLPAIVPAARKATAAVIFLHGLGDTGHGWAEAFAGIRSSHIKYICPHAPVRPVTLNMNVAMPSWFDIIGLSPDSQEDESGIKQAAENIKALIDQEVKNGIPSNRIILGGFSQGGALSLYTALTTQQKLAGVTALSCWLPLRASFPQGPIGGANRDISILQCHGDCDPLVPLMFGSLTVEKLKTLVNPANVTFKTYEGMMHSSCQQEMMDVKQFIDKLLPPID
Enzyme Length 230
Uniprot Accession Number O75608
Absorption
Active Site ACT_SITE 119; /note=Charge relay system; /evidence=ECO:0000269|PubMed:19439193; ACT_SITE 174; /note=Charge relay system; /evidence=ECO:0000305|PubMed:11080636; ACT_SITE 208; /note=Charge relay system; /evidence=ECO:0000305|PubMed:11080636
Activity Regulation ACTIVITY REGULATION: Inhibited by palmostatin-B, leading to impair depalmitoylating of Ras. {ECO:0000269|PubMed:20418879}.
Binding Site
Calcium Binding
catalytic Activity CATALYTIC ACTIVITY: Reaction=H2O + S-hexadecanoyl-L-cysteinyl-[protein] = H(+) + hexadecanoate + L-cysteinyl-[protein]; Xref=Rhea:RHEA:19233, Rhea:RHEA-COMP:10131, Rhea:RHEA-COMP:11032, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:29950, ChEBI:CHEBI:74151; EC=3.1.2.22; Evidence={ECO:0000269|PubMed:22399288}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoyl-sn-glycero-3-phosphocholine + H2O = H(+) + hexadecanoate + sn-glycerol 3-phosphocholine; Xref=Rhea:RHEA:40435, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16870, ChEBI:CHEBI:72998; Evidence={ECO:0000269|PubMed:19439193};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40436; Evidence={ECO:0000305|PubMed:19439193}; CATALYTIC ACTIVITY: Reaction=a 1-(9Z-octadecenoyl)-2-acyl-sn-glycero-3-phosphocholine + H2O = (9Z)-octadecenoate + a 2-acyl-sn-glycero-3-phosphocholine + H(+); Xref=Rhea:RHEA:41720, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:57875, ChEBI:CHEBI:78421; Evidence={ECO:0000269|PubMed:21393252};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41721; Evidence={ECO:0000305|PubMed:21393252};
DNA Binding
EC Number 3.1.2.-; 3.1.2.22
Enzyme Function FUNCTION: Acts as a acyl-protein thioesterase (PubMed:19439193, PubMed:20418879). Hydrolyzes fatty acids from S-acylated cysteine residues in proteins such as trimeric G alpha proteins or HRAS (PubMed:20418879). Has depalmitoylating activity toward KCNMA1 (PubMed:22399288). Could also depalmitoylate ADRB2 (PubMed:27481942). Acts as a lysophospholipase and hydrolyzes lysophosphatidylcholine (lyso-PC) (PubMed:19439193). Also hydrolyzes lysophosphatidylethanolamine (lyso-PE), lysophosphatidylinositol (lyso-PI) and lysophosphatidylserine (lyso-PS) (By similarity). Has much higher thioesterase activity than lysophospholipase activity (PubMed:19439193). Contributes to the production of lysophosphatidic acid (LPA) during blood coagulation by recognizing and cleaving plasma phospholipids to generate lysophospholipids which in turn act as substrates for ENPP2 to produce LPA (PubMed:21393252). {ECO:0000250|UniProtKB:P70470, ECO:0000269|PubMed:19439193, ECO:0000269|PubMed:20418879, ECO:0000269|PubMed:21393252, ECO:0000269|PubMed:22399288, ECO:0000269|PubMed:27481942}.
Temperature Dependency
PH Dependency BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 7.4 for the thioesterase activity. {ECO:0000269|PubMed:19439193};
Pathway
nucleotide Binding
Features Active site (3); Alternative sequence (1); Beta strand (12); Chain (1); Erroneous initiation (1); Helix (9); Modified residue (1); Mutagenesis (1); Natural variant (1); Sequence conflict (1); Turn (1)
Keywords 3D-structure;Acetylation;Alternative splicing;Cell membrane;Cytoplasm;Endoplasmic reticulum;Fatty acid metabolism;Hydrolase;Lipid metabolism;Membrane;Nucleus;Reference proteome
Interact With Q08379; Q5VUG0
Induction
Subcellular Location SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19439193}. Cell membrane {ECO:0000269|PubMed:19439193}. Nucleus membrane {ECO:0000269|PubMed:19439193}. Endoplasmic reticulum {ECO:0000269|PubMed:19439193}. Note=Shows predominantly a cytoplasmic localization with a weak expression in the cell membrane, nuclear membrane and endoplasmic reticulum. {ECO:0000269|PubMed:19439193}.
Modified Residue MOD_RES 224; /note=N6-acetyllysine; /evidence=ECO:0000250|UniProtKB:P97823
Post Translational Modification
Signal Peptide
Structure 3D X-ray crystallography (6)
Cross Reference PDB 1FJ2; 5SYM; 6QGN; 6QGO; 6QGQ; 6QGS;
Mapped Pubmed ID 16000296; 17353931; 19465924; 20064372; 20685872; 21779505; 21905185; 21905186; 22144181; 22623428; 23396970; 25670628; 25849916; 2661017; 26701913; 26771141; 27748579; 28630138; 29295957; 29311131; 29362370; 29648538; 30431103; 30482805; 33707782;
Motif
Gene Encoded By
Mass 24,670
Kinetics BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=27.3 uM for lysophosphatidylcholine for lysophospholipase activity {ECO:0000269|PubMed:19439193}; KM=3.49 uM for thioesterase activity {ECO:0000269|PubMed:19439193}; Vmax=1.62 umol/min/mg enzyme toward lysophosphatidylcholine for lysophospholipase activity {ECO:0000269|PubMed:19439193}; Vmax=27.3 umol/min/mg enzyme for thioesterase activity {ECO:0000269|PubMed:19439193};
Metal Binding
Rhea ID RHEA:19233; RHEA:40435; RHEA:40436; RHEA:41720; RHEA:41721
Cross Reference Brenda 3.1.2.22;