Higher eukaryotes have many distinct esterases. The different types include those that act on carboxylic esters (EC 3.1.1). Carboxyl-esterases have been classified into three categories (A, B and C) on the basis of differential patterns of inhibition by organophosphates. Here are B type. WARNING There is no Plant carboxylesterases in this family except an EST from sorgho (sorbi-cxest) which could be a contaminant. Plant carboxylesterases do not possess SEDCLYLN and are included in a specific family: Plant_carboxylesterase. This family corresponds to the Carbohydrate Esterase family CE10 in CAZy - Carbohydrate-Active enZYmes database (CE_10). For bacterial enzymes this family correspond to family VII of the classification of Arpigny and Jaeger (1999)
Carboxylesterases of insects have been subdivided in clades A to M (Claudianos 2006 Ranson 2002). With the Dietary class (clades ABC), the Pheromone/hormone processing class (clades D to G), the Neuro/developmental class (H to M). The present family Carb_B_Arthropoda corresponds to clades ABC. Members of these clades are important in detoxifixtion of insecticides .Gene amplifications or point mutations leading to resistance. Clades D to M have their own family (AChE, JHE, Glutactin Neuroligin, Neurotactin). This family was extracted from the previous Carboxylesterase COesterase family. This family corresponds to the Carbohydrate Esterase family CE10 in CAZy - Carbohydrate-Active enZYmes database (CE_10).
This family was extracted from the previous Carboxylesterase COesterase family. Not all bacteria possess esterase with the SEDCLYLN signature. This family corresponds to the Carbohydrate Esterase family CE10 in CAZy - Carbohydrate-Active enZYmes database (CE_10). As bacterial enzymes this family correspond to family VII of the classification of Arpigny et al 1999
This family was extracted from the previous Carboxylesterase COesterase family. This family corresponds to the Carbohydrate Esterase family CE10 in CAZy - Carbohydrate-Active enZYmes database (CE_10).
This family was extracted from the previous Carboxylesterase COesterase family. This family corresponds to the Carbohydrate Esterase family CE10 in CAZy - Carbohydrate-Active enZYmes database (CE_10). Mammalian liver carboxylesterases (CESs; EC 3.1.1.1) hydrolyze various xenobiotics and endogenous substrates with ester, thioester, or amide bonds and are thought to function mainly in drug metabolism and detoxication of harmful chemicals. CES1 is also responsible for hydrolysis of stored cholesterol esters in macrophage foam cells and release of free cholesterol for high density lipoprotein-mediated cholesterol efflux
This family was extracted from the previous Carboxylesterase COesterase family. This family corresponds to the Carbohydrate Esterase family CE10 in CAZy - Carbohydrate-Active enZYmes database (CE_10).
This family was extracted from the previous Carboxylesterase COesterase family. This family corresponds to the Carbohydrate Esterase family CE10 in CAZy - Carbohydrate-Active enZYmes database (CE_10). A subset of this family is isolated as Esterase CM06B1-like family in Interpro IPR043187.
This family was extracted from the previous Carboxylesterase COesterase family. it contains putative esterase from eucaryotes (not insects nematodes or chordates)
The human lactating mammary gland and pancreas produce a lipolytic enzyme, carboxyl-ester lipase, earlier called bile salt-stimulated lipase. Carboxyl-ester lipase is a major component of pancreatic juice and is responsible for the hydrolysis of cholesterol esters as well as a variety of other dietary esters. The enzyme is activated when mixed with bile salts, and plays an important role in the digestion of milk fat in newborn infants. This enzyme combines properties of esterases (activity on esters soluble in water) and lipases (activity on insoluble long chain acylglycerols) Numerous repeats at the c-term excluded in ESTHER (only n-term Pfam A COesterase 1 544)
This family was extracted from the previous Carboxylesterase COesterase family. Carboxylesterase, type B (COesterase) is very successful in fungi. Grouped with Lipase_3 in Family Fungal lipases in scop database. This family corresponds to the Carbohydrate Esterase family CE10 in CAZy - Carbohydrate-Active enZYmes database (CE_10) LED_Database abH03 abH02. The presence of a water/lipid interface dramatically enhances the hydrolytic activity of lipases. The activation is associated with a conformational change. The Ser-His-Asp/Glu catalytic triad is occluded by a polypeptide flap (lid) and is not exposed to the solvent until the lid is open. A protein of this family lacking the catalytic serine is a dirigent protein which controls the stereoselectivity of multicopper oxidase(VdtB)-catalyzed phenol coupling in viriditoxin biosynthesis (Hu et al. 2019)
Juvenile hormone JH is an insect hormone containing an alpha,beta-unsaturated ester consisting of a small alcohol and long hydrophobic acid. JH degradation is required for proper insect development. One pathway of this degradation is through juvenile hormone esterase JHE which cleaves the JH ester bond to produce methanol and JH acid. Another way of degradation of JH is epoxyde hydrolysis. Most insect species contain only juvenile hormone (JH) III. To date JH 0, JH I, and JH II have been identified only in the Lepidoptera (butterflies and moths). The form JHB3 (JH III bisepoxide) appears to be the most important JH in the Diptera, or flies. Certain species of crustaceans have been shown to produce and secrete methyl farnesoate, which is juvenile hormone III lacking the epoxide group. Methyl farnesoate is believed to play a role similar to that of JH in crustaceans. In drosophila DmJHE is the hormone esterase with precise regulation and highly specific activity for its substrate, juvenile hormone. DmJHEdup is an odorant degrading esterase (ODE) responsible for processing various kairomones in antennae
Acetylcholinesterase (ACHE; EC 3.1.1.7) controls synaptic and neurohumoral cholinergic activity by hydrolyzing the neurotransmitter acetylcholine. ACHE function relies on precise regulation of its expression and localization. In particular, alternative splicing of the 3-prime region of ACHE results in ACHE isoforms with distinct C-terminal peptides that determine posttranslational maturation and oligomeric assembly
Acetylcholinesterase (ACHE; EC 3.1.1.7) controls synaptic and neurohumoral cholinergic activity by hydrolyzing the neurotransmitter acetylcholine. ACHE function relies on precise regulation of its expression and localization. In particular, alternative splicing of the 3-prime region of ACHE results in ACHE isoforms with distinct C-terminal peptides that determine posttranslational maturation and oligomeric assembly. Acetylcholinesterase is also found on the red blood cell membranes, where it constitutes the Yt blood group antigen.
Acylcholine acylhydrolase, Butyrylcholine esterase, Choline esterase II, Pseudocholinesterase. Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters. BChE deficiency is a metabolic disorder characterized by prolonged apnoea after the use of certain anesthetic drugs, including the muscle relaxants succinylcholine or mivacurium and other ester local anesthetics.Various autosomal recessive mutations of the gene exist in human population
Analysis of the complete genome sequences of numerous representatives of the various metazoan phyla show that moderate amplification of cholinesterase genes is not uncommon in molluscs, echinoderms, hemichordates, prochordates or lepidosauria. Amplification of acetylcholinesterase genes is also a feature of parasitic nematodes or ticks. This family is now called Cholinesterase like. It also contains sequences very close to AChE but which are either incomplete or are missing W84 or one of the residue of the catalytic triad or are pseudogenes with deletions or errors of conceptual splicing Before this family was called Dictyostelium_crys as it contained only Dict proteins. These proteins have an active site serine and have probably an esterase activity but are in membrane-enclosed crystals and probably have non catalytic functions.
This family contains genes/protein of the COesterase group which lack some of the active site residues (neuroligins, neurotactin, gliotactin, glutactin)
Gliotactin, a transmembrane protein on peripheral glia, is required to form the blood-nerve barrier in Drosophila. It is a marker of tricellular junctions, is necessary for septate junction development in Drosophila. Gliotactin and Discs large form a protein complex at the tricellular junction of polarized epithelial cells in Drosophila. The intracellular domain of gliotactin, is natively unfolded. Control of Gliotactin localization and levels by tyrosine phosphorylation and endocytosis is necessary for survival of polarized epithelia
Insect specific protein. Glutactin has a signal peptide and an amino domain of greater than 500 residues that strongly resembles acetylcholine esterases and other serine esterases, but lacks the catalytically critical serine residue. It is located at embryonic basement membranes, particularly to the sequentially invaginated envelope of the central nervous system, muscle apodemes and dorsal median cell processes. Ectopic expression of Glutactin inhibits synapse formation by motor neurons that normally innervate M12 muscle. Only the N-terminal part of Glutactin is a member of the alpha/beta hydrolase family. The C-terminal part is not included in ESTHER
Neuroligins constitute a family of proteins thought to mediate cell-to-cell interactions between neurons. Neuroligins function as ligands for the neurexin family and MADD-4. This interaction is necessary for GABA receptors clustering. Mammals have four Nlgn proteins, with the Nlgn3 and Nlgn4 gene in humans localised to the X-chromosome. In humans, the Nlgn4 gene is complemented on the Y-chromosome by a similar Nlgn4Y gene.(from OMIM) In 2 brothers with autism, one with typical autism and the other with Asperger syndrome, Jamain et al. (2003) identified a frameshift mutation (1186T) in the human-NLGN4X gene, resulting in a stop codon at position 396 and premature truncation of the protein before the transmembrane domain. The mutation was present in the mother and absent in an unaffected brother and 350 controls. See other contradictory results Gauthier et al. Vincent et al., but other mutations found Laumonnier et al. Yan et al. Incomplete penetrance suspected for some mutations. In 2 brothers with autism, one with typical autism and the other with Asperger syndrome, Jamain et al. (2003) identified a mutation R451C in the human-NLGN3 gene. arg451 in NLGN3, arg386 in BCHE, and arg395 in ACHE are conserved in mammalian species. In cellular transfection studies, De Jaco et al. (2006) inserted mutations homologous to the NLGN3 R451C mutation in BCHE and ACHE cDNAs and found that these mutations resulted in endoplasmic reticulum retention of the 2 proteins, similar to that observed with the NLGN3 R451C mutant protein. Tabuchi et al. (2007) introduced the R451C substitution in neuroligin-3 into mice. R451C mutant mice showed impaired social interactions but enhanced spatial learning abilities. Unexpectedly these behavioral changes were accompanied by an increase in inhibitory synaptic transmission with no apparent effect on excitatory synapses. Deletion of neuroligin-3, in contrast, did not cause such changes, indicating that the R451C substitution represents a gain-of-function mutation. Tabuchi et al. (2007) concluded that increased inhibitory synaptic transmission may contribute to human autism spectrum disorders and that the R451C knockin mice may be a useful model for studying autism-related behaviors. Recently Venkatesh et al. showed that neuronal activity promotes glioma growth through Neuroligin-3 secretion. Recently Neuroligin 2 mutations were associated with anxiety, autism, intellectual disability, hyperphagia, and obesity.Many mutations on X-linked cell NLGN4X result in ASD or intellectual disability. NLGN4Y cannot compensate for the functional deficits due to NLGN4X mutations (obsolete entries: Interpro IPR030022 Neuroligin-1, IPR030023 Neuroligin-2, IPR030024 Neuroligin-3 IPR030025 Neuroligin-4)
Only the C-terminal part of Neurotactin is a member of the alpha/beta hydrolase family. The N-terminal part of Neurotactin has low complexity is desordered and is intracellular. Neurotactin is found only in arthropods Neurotactin is only detected during cell proliferation and differentiation, and it is found mainly in neural tissue and also in mesoderm and imaginal discs. Neurotactin has a large cytoplasmic domain rich in charged residues and an extracellular domain similar to cholinesterase that lacks the active site serine required for esterase activity. Amalgam is a ligand for the transmembrane receptor neurotactin and is required for neurotactin-mediated cell adhesion and axon fasciculation in Drosophila. Mutants of neurotactin revealed specific requirements for neurotactin during axon outgrowth, fasciculation, and guidance.
Among COesterase PF00135 a number of proteins seem to lack active site residues but have not yet been characterized. They are not related to the known families of non-catalytic COesterase (neuroligins, neurotactin, gliotactin, glutactin) They could be pseudo genes or sequencing errors
Only the C-terminal part of thyroglobulin is a member of the alpha/beta hydrolase family, here starting with the first G in cholinesterase 2206 (aa numbering in human thyroglobulin). The N-terminal part of thyroglobulin is made of three domains, labeled I to III, that encompass 10 repeats of a ca. 65 amino acid residues known as the Tg type-1 repeat PF00086 PS00484 IPR011641 IPR000716 not included in ESTHER. Thyroglobulin is the glycoprotein precursor to the thyroid hormones T3 (triiodothyronine) and T4 (tetraiodothyronine). It has a molecular mass of 660 kD, with 2 identical subunits, yet its complete hydrolysis yields only 2 to 4 molecules of T3 and T4. The protein contains a 19-amino acid signal peptide followed by 2,748 residues. Van Ommen (1987) suggested that defects in the TG gene can cause either dominant or recessive disorders depending on the nature of the defect. When the gene is absent or at least when no thyroglobulin is synthesized, the disorder is likely to be recessive, whereas the presence of an abnormal subunit leads to a dominantly inherited disorder. The explanation for this is that in a dimeric protein such as thyroglobulin, 75% of the dimers in heterozygotes will contain 1 or more abnormal subunits. This should profoundly disturb thyroglobulin metabolism, since this protein fulfills a dual storage/catalytic role as a dimer, is present in bulk quantities (100 mg Tg/g thyroid mass), and needs to be exocytosed, iodinated, endocytosed, and degraded. EnsemblClone AF230666, EnsemblContig AC079020.2.132816.152274, AF235100_2 gene chromosome 8 clone PAC 98A24 map 8q24.3. there is a small gene with only a little bit of thyroglobuline just 3' of the real gene AC069434.7.189089.192039 ENST00000254617 ENSG00000132287. Three out of five iodination sites are in the cholinesterase homologous domain 2573 (In T4), 2587 (In T4),2766 (In T3)
AADAC Arylacetamide deacetylase displays cellular triglyceride lipase activity in liver, increases the levels of intracellular fatty acids derived from the hydrolysis of newly formed triglyceride stores and plays a role in very low-density lipoprotein assembly. Displays serine esterase activity in liver. Deacetylates a variety of arylacetamide substrates, including xenobiotic compounds and procarcinogens, converting them to the primary arylamide compounds and increasing their toxicity. NCEH1 KIAA1363 AADACL1 NCEH1 neutral cholesterol ester hydrolase 1.is highly expressed in invasive cancer cells and is the major protein in mouse brain diethylphosphorylated . Sequence similarities between hormone-sensitive lipase and prokaryotic enzymes was dicovered by Langin and Holm and Hemila et al.
Extracted from Hormone sensitive lipases. BD-FAE: The function of many members may differ from the one of the representavive used to describe the family in the PFAM database. (from PFAM): This family represents a novel bifunctional feruloyl and acetyl xylan esterase (BD-FAE, previously known as bifunctional carbohydrate esterase (CE)), which is active on complex natural xylans and was identified as the basis of a monophyletic clade gathering all homologs identified in PULs (polysaccharide utilisation loci) predicted to act on xylan. It adopts an alpha-beta-hydrolase fold with the catalytic triad Ser-Asp-His. This new family of proteins is a new candidate for biomass processing due to its capacity to remove ferulic acid and acetic acid from natural corn and birchwood xylan substrates. In PFAM database it includes family Tannase_Bact and family Est9X which are separate families in ESTHER. Feruloyl esterases are distributed in different sub-classes type-A B C,D and E and fall respectively in the following families. Type-A in Lipase_3, Type-B in Esterase_phb (PHB depolymerase), Type-C in Tannase, Type-D in FaeC, Type-E in A85-Feruloyl-Esterase, Type-F in BD-FAE
Bacterial esterases. Fang et al. described a novel esterase from a marine metagenomic library exhibiting high salt tolerance. The enzyme is essentially active on pNP-C2 C4 and C6. The family is extracted from 6_AlphaBeta_hydrolase. This family differs from all the families of the Arpigny Jaeger classification.
Sequences of lipases from metagenomic library were grouped in a new subset of Alphabeta hydrolase fold-3 (Arpigny_Jaeger Family_IV). Most sequences have a G(TDC)SA(G)G motif encompassing the active site serine.
Sequence similarities between hormone-sensitive lipase and prokaryotic enzymes was dicovered by Langin and Holm and Hemila et al.. The family Corresponds to the Pfam entry Abhydrolase_3. For bacterial enzymes this family correspond to family IV of the classification of Arpigny et al 1999
Kynurenine formamidase (EC:3.5.1.9) catalyses the hydrolysis of N-formyl-L-kynurenine to L-kynurenine, the second step in the kynurenine pathway of tryptophan degradation. It is required for elimination of toxic metabolites
No plant Carboxylesterase show the SEDCLYLN motif (prosite PS00941). These carboxylesterase are related to the Hormone sensitive lipase. Gibbereline Insensitive Dwarf1 GID1 has a primary structure similar to that of the hormone-sensitive lipase. Gibberellins (GAs) are tetracyclic, diterpenoid plant hormones, essential for many developmental processes in higher plants HSLs. The nuclear GA receptor evolved from an esterase. 2-hydroxyisoflavone dehydratase from leguminosae also belong to this family, in these particular enzymes the catalytic serine is replaced by threonine. In tulips tuliposide-converting enzyme (TCE) purified from tulip bulbs catalyzed the conversion of tuliposides to tulipalins.The lactone-forming carboxylesterases, specifically catalyzing intramolecular transesterification, but not hydrolysis
Sterol homeostasis in eukaryotic cells relies on the reciprocal interconversion of free sterols and steryl esters. In Saccharomyces cerevisiae (Baker's yeast) sterol acetylation requires the acetyltransferase Atf2, whereas deacetylation requires Say1, a membrane-anchored deacetylase with a putative active site in the ER lumen. Lack of Say1 results in the secretion of acetylated sterols into the culture medium, indicating that the substrate specificity of Say1 determines whether acetylated sterols are secreted from the cells or whether they are deacetylated and retained. In S. cerevisiae cells lacking Say1 or Atf2 are sensitive against the plant-derived allylbenzene eugenol and both Say1 and Atf2 affect pregnenolone toxicity, indicating that lipid acetylation acts as a detoxification pathway (old DUF2424)
This family of bacterial tannases close to hormone sensitive lipases, differs from the (Tannase) tannases and feruloyl esterase of fungi and bacteria grouped in the tannase family. The first structure described by Ren et al.Matoba et al. in this family presents a large cap domain inserted after the beta 7 strand of classical alpha/beta hydrolases. Tannases hydrolyze the galloyl ester bond in tannins to release gallic acid
This family has been recognized as alpha/beta hydrolase by Kamil et al. Previously associated with Lipoprotein_lipase family but is also close to phospholipase. vLIP may not serve as a traditional lipase enzyme, but the serine nucleophile position is essential in vivo for the viral functions of vLIP. Could be example of repurposing alpha/beta hydrolase fold toward a nonenzymatic role, possibly in lipid bonding
This family correspond to family I.1, I.2, I.3, I.5, I.6, (families I.4 and 1.7 are more related to Lipase_2) of the classification of Arpigny and Jaeger (1999).(also included in IPR000734) Also close to Lipase_2 (2lip). Pseudomonas cepacia lipase is in the same family of scop as 1I6W bacillus subtilis lipase).
This family corresponds to family I.3 of the classification of Arpigny and Jaeger (1999) The N-catalytic domain (residues 1370) contains the active site residues, Ser207, Asp255, and His313 4, 5. The C-domain contains several repeats of the RTX motif and a putative secretion signal near the C-terminus. The Cdomain contains two beta-roll motifs, laterally stacked together forming the so called beta-roll sandwich. The first beta-roll motif consists of residues 373417, containing five RTX repeats and binds three Ca2+ ions. The second beta-roll motif consists of residues 493-568, containing eight RTX repeats and binds five Ca2+ ions. HemolysinCabind (PF00353). This family contains Polyurethanases (PURase)
This family correspond to family I.5 of the classification of Arpigny and Jaeger (1999) and abH15 of the LED database. It includes lipases from gram positive bacteria, organic-solvent tolerant, showing thermoalkalophilic properties and high molecular weight resulting from extra domain where a zinc ion is coordinatively bound to the enzyme. The family also contains poly (butylene adipate-co-terephthalate)-hydrolyzing lipase from Pelosinus fermentans
This family correspond to family I.6 of the classification of Arpigny and Jaeger (1999). These lipases differ from other bacterial lipases. They present high phospholipase A1 activity. The substrate-binding cavity contains two large hydrophobic acyl chain-binding pockets and a shallow and more polar third pocket that is capable of binding either a (short) fatty acid or a phospholipid head-group.
The lead of this family is Candida antarctica (Trichosporon oryzae) (yeast) Lipase B. It was previously embedded in Lipase_3. The family corresponds to the _abH37 - Candida antarctica lipase like_ family of the LED database. Lipase B from Candida antarctica (CALB) has broad substrate specificity and high enantioselectivity. It can function in aqueous and organic environments and is used for a wide range of applications such as transesterification, and polymerization reactions, asymmetric synthesis PANTHER db family PTHR37574
Chlorophyllase (Chlase) enzyme involved in chlorophylle (Chl) degradation and catalyses the hydrolysis of ester bond to yield chlorophyllide and phytol. This family correspond to bacterial enzymes close to chlorophyllases of plant Chlorophyllase_Plant. The activity of these enzymes are related to cutinase and Poly-ethylene-therephthalate (PET) hydrolases
This family consists of several plant specific Chlorophyllase proteins (EC: 3.1.1.14). Chlorophyllase (Chlase) is the first enzyme involved in chlorophylle (Chl) degradation and catalyses the hydrolysis of ester bond to yield chlorophyllide and phytol The family includes both plant bacteria and Amphioxus members. However Chlorophyllase is not localized to plastids, and double knockout mutant plants still are able to degrade chlorophyll during leaf senescence. So pheophytinase is a new pathway. Chlorophyllase could be more important in fruit rippening. Some bacterial enzyme are close to plant chlorophyllases but are now separated in another family Chlorophyllase. (Few sponge or marine invertebrates protein included). A structure-function analysis of chlorophyllase reveals a mechanism for activity regulation dependent on disulfide bonds(Jo et al.)
Pancreatic, hepatic and gastric/lingual lipase are closely related to each other and to lipoprotein lipase (EC: 3.1.1.34), which hydrolyses triglycerides of chylomicrons and very low density lipoproteins (VLDL). Familial human hepatic lipase deficiency is a rare recessive disorder Two variants (S267F and T383M) are rare mutations found to date only in HL deficient subjects and their relatives. Of the six HL variants described to date, only S267F and T383M are associated with hyperlipidemia. human-LIPC. The disease is characterised by premature atherosclerosis and abnormal circulating lipoproteins
Phospholipase A(1) (PLA(1)) is an enzyme that hydrolyzes phospholipids and produces 2-acyl-lysophospholipids and fatty acids and is conserved in a wide range of organisms. Included in this family are Vespid venom allergen phospholipase A1. Vespid phospholipase A1 (vPLA1) is one of the primary venom components with local inflammatory effects. In addition to causing allergic reactions, vPLA1 can hydrolyze the sn-1 fatty acids in phospholipids and convert them into their corresponding lyso compounds. vPLA1 may disrupt the phospholipid packing of biological membranes, causing severe hemolysis and leading to cardiac dysfunction and death in animals
This family groups insect lipases close to mammalian pancreatic, hepatic and gastric/lingual lipase which are closely related to each other and to lipoprotein lipase (EC: 3.1.1.34), which hydrolyses triglycerides of chylomicrons and very low density lipoproteins (VLDL). These are neutral lipases distinct from Acidic lipases and higher dipteran yolk proteins
Triglyceride lipases are lipases that hydrolyse ester linkages of triglycerides. These lipases are widely distributed in animals, plants and prokaryotes. This family was also called class 3 lipases as they are only distantly related to other lipase families. In some fungi DDHD domain Pfam PF02862 180 residues long containing four conserved residues that may form a metal binding site is associated with the Lipase_3. Bacterial enzymes (LipG Lee et al. 2006) belong to family XI of the classification of Arpigny and Jaeger 1999. The (phospho)lipase of F.solani has the highest microbial activity on galactolipids Jallouli et al. Feruloyl esterases are enzymes produced by micro-organisms to deconstruct plant cell walls by hydrolyzing phenolic groups involved in the cross-linking of arabinoxylan to other polymeric structures. The non-modular type-A feruloyl esterase from Aspergillus niger AnFaeA is similar to fungal lipases and different from other feruloyl esterases. Feruloyl esterases are distributed in different sub-classes type-A B C,D and E and fall respectively in the following families. Type-A in Lipase_3, Type-B in Esterase_phb (PHB depolymerase), Type-C in Tannase, Type-D in FaeC, Type-E in A85-Feruloyl-Esterase, Type-F in BD-FAE
Lipoprotein lipase (LPL) is a key enzyme of lipid metabolism that hydrolyses triglycerides, providing free fatty acids for cells and affecting the maturation of circulating lipoproteins. The enzyme is thought to play a role in the development of obesity and atherosclerosis. Defects in LPL are a cause of familial chylomicronemia syndrome (or type I hyperlipoproteinemia) and also of a form of deficiency characterised by hypertriglyceridemia. Familial chylomicronemia is a recessive disorder usually manifesting in childhood. On a normal diet, patients often present with abdominal pain, hepatosplenomegaly, lipemia retinalis, eruptive xanthomata, and massive hypertriglyceridemia, sometimes complicated with acute pancreatitis. Endothelial lipase (encoded by the LIPG gene) regulates the circulating level of high density lipoprotein cholesterol (HDL-C). It can also form a molecular bridge between endothelial cells and lipoproteins or circulating macrophages through interaction with heparan sulfate proteoglycans. This nonenzymatic action can increase cellular lipoprotein uptake and monocyte adhesion and contribute to atherosclerosis. LPL is a secreted glycoprotein that contains five disulfide bonds and requires an endoplasmic reticulum (ER) protein, lipase maturation factor 1 (LMF1), to successfully fold and traffic out of the ER to the Golgi. LPL is sorted into vesicles in an inactive state: helical LPL oligomer. LPL secretion is mediated by Syndecan-1 (SDC1), a heparan sulfate proteoglycan (HSPG). Stored LPL can be secreted into the interstitial space, where it interacts with HSPGs that bind to the multiple heparin binding sites on each LPL molecule . LPL is next bound by glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) and transported into the capillary, where it acts on chylomicrons and very-low-density lipoproteins (VLDLs) to hydrolyze packaged triglycerides and release FFAs. The angiopoietin-like (ANGPTL) family of proteins inhibit LPL in different tissues. Leth-Espensen et al. publish that the intrinsic instability of the hydrolase domain of lipoprotein lipase facilitates its inactivation by ANGPTL4-catalyzed unfolding. Inverse effects of APOC2 and ANGPTL4 on the conformational dynamics of lid-anchoring structures in lipoprotein lipase is published by Kumari et al.
Pancreatic, hepatic and gastric/lingual lipase are closely related to each other and to lipoprotein lipase (EC: 3.1.1.34), which hydrolyses triglycerides of chylomicrons and very low density lipoproteins (VLDL). Pancreatic lipase (triacylglycerol acylhydrolase, EC: 3.1.1.3) plays a key role in dietary fat absorption by hydrolysing dietary long chain triacyl-glycerol to free fatty acids and monoacylglycerols in the intestinal lumen. The activity of lipase is stimulated by colipase in the presence of bile acids. Congenital pancreatic lipase deficiency is a rare, monoenzymatic form of exocrine pancreatic failure. Patients have oily/greasy stools from infancy or early childhood and the absence of discernable pancreatic disease. The pancreatic lipase-related protein show no significant catalytic activity on any of the substrates tested di and tri-glycerides phospholipids. Introducing the double mutation Val 178 Ala and Ala 180 Pro into the human pancreatic RP1 HPLRP1 gene yielded an enzyme is kinetically active on triglycerides. The guinea pig pancreatic lipase-related protein 2 (GPLRP2) differs from classical pancreatic lipases in that it displays both lipase and phospholipase A1 activities; classical pancreatic lipases have no phospholipase activity. human-PNLIPRP2 adopt in solution an open lid conformation which creates a large cavity capable of accommodating the galactose polar head of galactolipids (galactolipase)
Phospholipase A(1) (PLA(1)) is an enzyme that hydrolyzes phospholipids and produces 2-acyl-lysophospholipids and fatty acids and is conserved in a wide range of organisms. Hypotrichosis, or woolly hair with or without hypotrichosis hypotrichosis (deficiency of hair growth), can be caused by homozygous or compound heterozygous mutation in the LIPH (human-LIPH) gene on chromosome 3q27 (not hepatic lipase: human-LIPC). Other mammalian enzymes that exhibit PLA(1) activity in vitro are hepatic lipase HL endothelial lipase EL and pancreatic lipase-related protein 2 PLRP2 and belong to alpha/beta hydrolase superfamily.
Enhanced Disease Susceptibility 1 (EDS1), an essential component of R gene-mediated disease resistance. The Arabidopsis EDS1 (arath-eds1) and PAD4 (arath-F22O6.190) genes encode lipase-like proteins that function in resistance (R) gene-mediated and basal plant disease resistance. EDS1 can dimerize and interact with PAD4. EDS1 (arath-eds1) and PAD4 (arath-F22O6.190) genes encode lipase-like proteins that function in resistance (R) gene-mediated and basal plant disease resistance. EDS1 can dimerize and interact with PAD4 or with SAG101 (arath-At5g14930). This family is extracted from the Lipase3 gene family. The C-terminal domain known as the EP domain and its interface consists of hydrophobic interactions, salt bridges, and an extensive hydrogen bonding network. Plants utilise intracellular nucleotide-binding, leucine-rich repeat (NLR) immune receptors to detect pathogen effectors and activate local and systemic defence. NRG1 and ADR1 'helper' NLRs (RNLs) cooperate with enhanced disease susceptibility 1 (EDS1), senescence-associated gene 101 (SAG101) and phytoalexin-deficient 4 (PAD4) lipase-like proteins to mediate signalling from TIR domain NLR receptors (TNLs). Two distinct modules (NRG1/EDS1/SAG101 and ADR1/EDS1/PAD4) mediate TNL receptor defence signalling. (In the seed alignment and the HMM alignement the EP domain (not alpha/beta hydrolase domain) is excluded)
Family close to Lipase_3. The DEFECTIVE IN ANTHER DEHISCIENCE gene encodes a novel phospholipase A1 catalyzing the initial step of jasmonic acid biosynthesis, which synchronizes pollen maturation, anther dehiscence, and flower opening in Arabidopsis. AtDSEL, an Arabidopsis cytosolic DAD1-like acylhydrolase, is involved in negative regulation of storage oil mobilization during seedling establishment. This family is close to Plant_lipase_EDS1-like and belongs to Lipase_3 family
This family differs substantially from the cutinase acetyl-xylan esterase family (cutinase monofunctional). Several cutinases from the genus Thermobifida act on biodegradable plastics such as synthetic polyesters. Not all cutinases can degrade polyester plastics. Aerial plant organs are protected by a cuticle composed of an insoluble polymeric structural compound, cutin, which is a polyester composed of hydroxy and hydroxyepoxy fatty acids. Cutinases are lipases with a specificity for p-nitrophenyl acyl esters with short chain acyl group. This family was extracted from the Bacterial_lipase family which is close to PAF-Acetylhydrolase family. Streptomyces exfoliatus lipase (1JFR) Pseudomonas mendocina lipase (2FX5) are included in this family. This family correspond to family III of the classification of Arpigny et al 1999. Polyethylene terephthalate degrading hydrolase/PET-hydrolase/PET Hydrolase. Two enzymes in Ideonella sakaiensis (for example) act on PET (Poly ethylene terephthalate): idesa-peth from Polyesterase-lipase-cutinase family and idesa-mheth which acts on extremity of PET (Exo-PETase Function PET hydrolase PET-Hydrolase) and on MHET the product of hydrolysis of PET. MHETase belongs to the Tannase family
Family extracted from Lipase_3. (from InterPro) This family includes triacylglycerol lipase OBL1 from Arabidopsis thaliana and Nicotiana tabacum, which are homologues of the acid lipase from castor bean (RcOBL1). OBL1 is an acid GXSXG - lipase localized to lipid droplets that can hydrolyse a range of triacylglycerols without a clear preference for acyl-chains. It can also cleave 1,2-diacylglycerol, 1,3-diacylglycerol and 1-monoacylglycerol, but not phosphatidylcholine, phosphatidylethanolamine, or sterol esters. It is required for pollen tube growth. Triacylglycerol hydrolysis by OBL1 may provide acyl groups for the synthesis of membrane lipids in growing pollen tubes
These proteins sometimes referred as vitellogenins are specific to higher dipters and are not evolutionnary related to the vitellogenins accumulated in oocytes of most oviparous animals
This family consists of abhydrolase domain-containing protein 16 A (ABHD16A). Function of its members is unknown. However, ABHD16A contains transmembrane domain and is a potential multi-pass membrane protein. BAT5 (HLA-B-associated transcript 5). Savinainen et al. showed hydrolysis of medium-chain saturated (C14:0), long-chain unsaturated (C18:1, C18:2, C20:4) monoacylglycerols (MAGs) and 15-deoxy-12,14-prostaglandin J2-2-glycerol ester (15d-PGJ2-G). Only marginal diacylglycerol (DAG), triacylglycerol (TAG), or lysophospholipase activity PANTHER PTHR12277:SF54 There are two genes ABHD16 A and B in amniotes. Shan et al. identified a nonsense mutation in the bovine ABHD16B associated with male subfertility in Holstein cattle. ABHD16B is involved in lipid biosynthesis in testis and is crucial for fertilization. ABHD16A deficiency causes a complicated form of hereditary spastic paraplegia associated with intellectual disability and cerebral anomalies (Lemire et al. 2021; Yahia et al. 2021; Miyake 2021). Substrates of ABHD include medium-chain saturated monoacylglycerols, 1-linoleylglycerol, 15-deoxy-delta12,14-prostaglandin J2-2-glycerol ester
Proteins of bacteria and fungi or uncategorised eukaryotes but not in animals or plants. The only sequence of viridi planta (Ricinus communis) might result from an horizontal transfer or a contamination. Although proteins in this family are uncharacterised they are likely to have an enzymatic activity. In mycpa-q73tu8 Mycobacterium paratuberculosis the catalytic triad would be Ser191, Asp259, His 289. The name of this family comes from Pfam but should not be confounded with family ABHD10 which is quite far related
This family corresponds partially to PF12695 (Abhydrolase_5), however as previously separated families existed this family does not includes epoxide hyrolase like families which are closely related to this family
This family corresponds partially to PF12695 (Abhydrolase_5). This undefined family is progressively shrinking as some families are extracted (recently: Extracel-MCL-phaZ and yjfP_esterase-like) One thermostable esterase containing an immunoglobulin-like domain is in the seed of the family. The immunoglobulin-like domain is found in other esterases that belong to another esterase families A85-IroE-IroD-Fes-Yiel. Not all the members of the 5_AlphaBeta_hydrolase possess this domain
Poly(aspartate) (PAA) is a bio-based, biocompatible, biodegradable alternative to polycarboxylate of poly(acrylate). Bacterial PAA-hydrolyzing enzyme can also perform synthesis of poly(alpha-ethyl beta-aspartate). This family is close to PHB depolymerase. The LpqC, poly(3-hydroxybutyrate) depolymerase from Bordetella parapertussis (CASP Target) (structure 3D0K) belongs to this family. Polyaspartic acid (PASA) is also a natural polymer as fragment of larger proteins with length up to 50 amino acids. Synthetic tPAA(thermally synthesized PAA) consists of beta-amide (70%) and alpha-amide,(30%) D- and L-aspartate units; the alpha- and beta-amide units are randomly distributed. PAA hydrolase-1 is an alpha beta hydrolase inhibited by PMSF and DFP. PAA hydrolase-2 is closer to metallo carboxypeptidase inhibited by DFP and PMSF
This family has many children sub-families. This family corresponds partially to PF12697 (Abhydrolase_6). However as previously separated families existed this family does not includes epoxide hyrolase like families which are closely related to this family. It also contains families that have their own Pfam entries but are closely related to this subset of the database
This family corresponds to the residual members of PF12697 Abhydrolase_6 not included in other subfamilies. Mostly badly characterized proteins. Many members of AlphaBeta_hydrolase family belong to this family and should soon be updated
ABHD11 is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region. ABHD11 is an enzyme acting on triacylglycerol. Many yeasts are able to produce ethyl acetate. Enzyme Eat1 from the yeast Wickerhamomyces anomalus showed alcohol acetyltransferase activity with ethanol and acetyl-CoA. Homologs of eat1 are responsible for most ethyl acetate synthesis in known ethyl acetate-producing yeasts, including S. cerevisiae, and are only distantly related to known alcohol acetyltransferases. Structure of ybfF protein from Escherichia coli (esterase of the large substrates, palmitoyl coenzyme A and malonyl coenzyme A) has been solved. Liu et al. published that: ABHD11 is critical for embryonic stem cell expansion, differentiation and lipid metabolic homeostasis. ABHD11-AS1 is An Emerging Long Non-Coding RNA (lncRNA) with Clinical Significance in Human Malignancies
Bacterial AHL-acylases (acyl homoserine lactonase) (AiiO, AidH) from genus Ochrobactrum and related bacteria are different from previously described AHL-acylases such as PvdQ, QuiP (P.aeriginosa) HacA HacB (P.syringea which belong to Ntn-hydrolase superfamily Czajkowski et al.) and different from AHL-lactonase of B. thuringensis and A. tumefasciens (which are metallo-beta lactamases). AHL-acylase inactivates N-acyl homoserine lactone (AHL) quorum sensing signal molecules (lactonases are also inactivating enzymes). AHL-acylases could be useful for the control of development of infections caused by pathogenic bacteria and their persistence in respective hosts. The three fungi sequences are genes without real introns (horizontal transfer?). There are other N-acyl homoserine lactonase (AiiA) not alpha/beta hydroalses but Metallo-B-lactamases
This entry represents a family of eukaryotic lipases, including gastric triacylglycerol lipase (LIPF) lysosomal acid lipase (LIPA) and LIPJ, LIPK, LIPM, LIPN. Mutations in LIPA cause Wolman disease, Cholesterol Ester Storage Disease, CESD and mutation in LIPN causes Late-Onset Form of Autosomal-Recessive Congenital Ichthyosis
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Block C 
Before this family was called Dictyostelium_crys as it contained only Dict proteins. These proteins have an active site serine and have probably an esterase activity but are in membrane-enclosed crystals and probably have non catalytic functions.