Palmitoyl protein thioesterases are enzymes (EC 3.1.2.22) that remove thioester-linked fatty acyl groups such as palmitate from modified cysteine residues in proteins or peptides during lysosomal degradation. PPT1 is responsible for the removal of a palmitate group from its substrate proteins, which may include presynaptic proteins like SNAP-25, cysteine string protein (CSP), dynamin, and synaptotagmin. PPT2 removes thioester-linked fatty acyl groups from various substrates including S-palmitoyl-CoA. PPT1 and -2 perform non-redundant roles in lysosomal thioester catabolism. Neuronal ceroid lipofuscinoses (NCL) represent a group of encephalopathies that occur in 1 in 12,500 children. Mutations in the palmitoyl protein thioesterase gene (human-PPT1) causing infantile neuronal ceroid lipofuscinosis. The most common mutation results in intracellular accumulation of the polypeptide and undetectable enzyme activity in the brain. Insensitive to commonly used serine-modifying reagents phenylmethylsulfonyl fluoride (PMSF) and diisopropylfluorophosphate. See paper of structure of bovine enzyme 1EXW (Das et al. 2000). PPT2 deficiency in a recent transgenic mouse model is associated with a form of neuronal ceroid lipofuscinosis, suggesting that PPT1 and -2 perform non-redundant roles in lysosomal thioester catabolism. Peptide based reversible inhibitors may have a role as chaperone that could facilitate the transport of mutant PPT1 variants to the lysosome where improved enzyme stability may be observed in the lower pH environment Family TE20 in ThYme database
Interpro : IPR002472 Palmitoyl protein thioesterase , IPR030295 Lysosomal thioesterase PPT2 , IPR030294 Palmitoyl-protein thioesterase 1
PIRSF : No PIRSF
Pdoc : No Pdoc
Pfam : PF02089 Palm_thioest
Prints : PR00414
EC Number : 3.1.2.22
Structures (5)
Genes Proteins in Palmitoyl-protein_thioesterase family (59)
Fragments of genes in Palmitoyl-protein_thioesterase family (13)
Structures in Palmitoyl-protein_thioesterase family (5)Substrates in Palmitoyl-protein_thioesterase family (1)
Inhibitors in Palmitoyl-protein_thioesterase family (7)
Title : Thioesterase enzyme families: Functions, structures, and mechanisms - Caswell_2021_Protein.Sci__ |
Author(s) : Caswell BT , de Carvalho CC , Nguyen H , Roy M , Nguyen T , Cantu DC |
Ref : Protein Science , : , 2021 |
Abstract : Caswell_2021_Protein.Sci__ |
ESTHER : Caswell_2021_Protein.Sci__ |
PubMedSearch : Caswell_2021_Protein.Sci__ |
PubMedID: 34921469 |
Title : Depalmitoylation by Palmitoyl-Protein Thioesterase 1 in Neuronal Health and Degeneration - Koster_2019_Front.Synaptic.Neurosci_11_25 |
Author(s) : Koster KP , Yoshii A |
Ref : Front Synaptic Neurosci , 11 :25 , 2019 |
Abstract : Koster_2019_Front.Synaptic.Neurosci_11_25 |
ESTHER : Koster_2019_Front.Synaptic.Neurosci_11_25 |
PubMedSearch : Koster_2019_Front.Synaptic.Neurosci_11_25 |
PubMedID: 31555119 |
Gene_locus related to this paper: human-PPT1 |
Title : Temporal Profiling Establishes a Dynamic S-Palmitoylation Cycle - Won_2018_ACS.Chem.Biol_13_1560 |
Author(s) : Won SJ , Martin BR |
Ref : ACS Chemical Biology , 13 :1560 , 2018 |
Abstract : Won_2018_ACS.Chem.Biol_13_1560 |
ESTHER : Won_2018_ACS.Chem.Biol_13_1560 |
PubMedSearch : Won_2018_ACS.Chem.Biol_13_1560 |
PubMedID: 29733200 |
Title : Infantile neuronal ceroid lipofuscinosis: follow-up on a Spanish series - Perez-Poyato_2012_Gene_499_297 |
Author(s) : Perez Poyato MS , Mila Recansens M , Ferrer Abizanda I , Domingo Jimenez R , Lopez Lafuente A , Cusi Sanchez V , Rodriguez-Revenga L , Coll Rosell MJ , Gort L , Poo Arguelles P , Pineda Marfa M |
Ref : Gene , 499 :297 , 2012 |
Abstract : Perez-Poyato_2012_Gene_499_297 |
ESTHER : Perez-Poyato_2012_Gene_499_297 |
PubMedSearch : Perez-Poyato_2012_Gene_499_297 |
PubMedID: 22387303 |
Gene_locus related to this paper: human-PPT1 |
Title : ThYme: a database for thioester-active enzymes - Cantu_2011_Nucleic.Acids.Res_39_D342 |
Author(s) : Cantu DC , Chen Y , Lemons ML , Reilly PJ |
Ref : Nucleic Acids Research , 39 :D342 , 2011 |
Abstract : Cantu_2011_Nucleic.Acids.Res_39_D342 |
ESTHER : Cantu_2011_Nucleic.Acids.Res_39_D342 |
PubMedSearch : Cantu_2011_Nucleic.Acids.Res_39_D342 |
PubMedID: 21045059 |
Title : Thioesterases: a new perspective based on their primary and tertiary structures. - Cantu_2010_Protein.Sci_19_1281 |
Author(s) : Cantu DC , Chen Y , Reilly PJ |
Ref : Protein Science , 19 :1281 , 2010 |
Abstract : Cantu_2010_Protein.Sci_19_1281 |
ESTHER : Cantu_2010_Protein.Sci_19_1281 |
PubMedSearch : Cantu_2010_Protein.Sci_19_1281 |
PubMedID: 20506386 |
Title : Palmitoyl:protein thioesterase (PPT1) inhibitors can act as pharmacological chaperones in infantile Batten disease - Dawson_2010_Biochem.Biophys.Res.Commun_395_66 |
Author(s) : Dawson G , Schroeder C , Dawson PE |
Ref : Biochemical & Biophysical Research Communications , 395 :66 , 2010 |
Abstract : Dawson_2010_Biochem.Biophys.Res.Commun_395_66 |
ESTHER : Dawson_2010_Biochem.Biophys.Res.Commun_395_66 |
PubMedSearch : Dawson_2010_Biochem.Biophys.Res.Commun_395_66 |
PubMedID: 20346914 |
Gene_locus related to this paper: human-PPT1 |
Title : The crystal structure of palmitoyl protein thioesterase-2 (PPT2) reveals the basis for divergent substrate specificities of the two lysosomal thioesterases, PPT1 and PPT2 - Calero_2003_J.Biol.Chem_278_37957 |
Author(s) : Calero G , Gupta P , Nonato MC , Tandel S , Biehl ER , Hofmann SL , Clardy J |
Ref : Journal of Biological Chemistry , 278 :37957 , 2003 |
Abstract : Calero_2003_J.Biol.Chem_278_37957 |
ESTHER : Calero_2003_J.Biol.Chem_278_37957 |
PubMedSearch : Calero_2003_J.Biol.Chem_278_37957 |
PubMedID: 12855696 |
Gene_locus related to this paper: human-PPT2 |
Title : Adult neuronal ceroid lipofuscinosis with palmitoyl-protein thioesterase deficiency: first adult-onset patients of a childhood disease - van Diggelen_2001_Ann.Neurol_50_269 |
Author(s) : van Diggelen OP , Thobois S , Tilikete C , Zabot MT , Keulemans JL , van Bunderen PA , Taschner PE , Losekoot M , Voznyi YV |
Ref : Annals of Neurology , 50 :269 , 2001 |
Abstract : van Diggelen_2001_Ann.Neurol_50_269 |
ESTHER : van Diggelen_2001_Ann.Neurol_50_269 |
PubMedSearch : van Diggelen_2001_Ann.Neurol_50_269 |
PubMedID: 11506414 |
Gene_locus related to this paper: human-PPT1 |
Title : The crystal structure of palmitoyl protein thioesterase 1 and the molecular basis of infantile neuronal ceroid lipofuscinosis - Bellizzi_2000_Proc.Natl.Acad.Sci.U.S.A_97_4573 |
Author(s) : Bellizzi JJ, 3rd , Widom J , Kemp C , Lu JY , Das AK , Hofmann SL , Clardy J |
Ref : Proc Natl Acad Sci U S A , 97 :4573 , 2000 |
Abstract : Bellizzi_2000_Proc.Natl.Acad.Sci.U.S.A_97_4573 |
ESTHER : Bellizzi_2000_Proc.Natl.Acad.Sci.U.S.A_97_4573 |
PubMedSearch : Bellizzi_2000_Proc.Natl.Acad.Sci.U.S.A_97_4573 |
PubMedID: 10781062 |
Gene_locus related to this paper: bovin-ppt , human-PPT1 |
Title : Structural basis for the insensitivity of a serine enzyme (palmitoyl-protein thioesterase) to phenylmethylsulfonyl fluoride - Das_2000_J.Biol.Chem_275_23847 |
Author(s) : Das AK , Bellizzi JJ, 3rd , Tandel S , Biehl E , Clardy J , Hofmann SL |
Ref : Journal of Biological Chemistry , 275 :23847 , 2000 |
Abstract : Das_2000_J.Biol.Chem_275_23847 |
ESTHER : Das_2000_J.Biol.Chem_275_23847 |
PubMedSearch : Das_2000_J.Biol.Chem_275_23847 |
PubMedID: 10801859 |
Gene_locus related to this paper: bovin-ppt2 , human-PPT1 |
Title : Mutations in the palmitoyl-protein thioesterase gene (PPT\; CLN1) causing juvenile neuronal ceroid lipofuscinosis with granular osmiophilic deposits - Mitchison_1998_Hum.Mol.Genet_7_291 |
Author(s) : Mitchison HM , Hofmann SL , Becerra CH , Munroe PB , Lake BD , Crow YJ , Stephenson JB , Williams RE , Hofman IL , Taschner PE , Martin JJ , Philippart M , Andermann E , Andermann F , Mole SE , Gardiner RM , O'Rawe AM |
Ref : Hum Mol Genet , 7 :291 , 1998 |
Abstract : Mitchison_1998_Hum.Mol.Genet_7_291 |
ESTHER : Mitchison_1998_Hum.Mol.Genet_7_291 |
PubMedSearch : Mitchison_1998_Hum.Mol.Genet_7_291 |
PubMedID: 9425237 |
Gene_locus related to this paper: human-PPT1 |
Title : Molecular genetics of palmitoyl-protein thioesterase deficiency in the U.S - Das_1998_J.Clin.Invest_102_361 |
Author(s) : Das AK , Becerra CH , Yi W , Lu JY , Siakotos AN , Wisniewski KE , Hofmann SL |
Ref : Journal of Clinical Investigation , 102 :361 , 1998 |
Abstract : Das_1998_J.Clin.Invest_102_361 |
ESTHER : Das_1998_J.Clin.Invest_102_361 |
PubMedSearch : Das_1998_J.Clin.Invest_102_361 |
PubMedID: 9664077 |
Gene_locus related to this paper: human-PPT1 |
Title : A novel insertion mutation (A169i) in the CLN1 gene is associated with infantile neuronal ceroid lipofuscinosis in an Italian patient - Santorelli_1998_Biochem.Biophys.Res.Commun_245_519 |
Author(s) : Santorelli FM , Bertini E , Petruzzella V , Di Capua M , Calvieri S , Gasparini P , Zeviani M |
Ref : Biochemical & Biophysical Research Communications , 245 :519 , 1998 |
Abstract : Santorelli_1998_Biochem.Biophys.Res.Commun_245_519 |
ESTHER : Santorelli_1998_Biochem.Biophys.Res.Commun_245_519 |
PubMedSearch : Santorelli_1998_Biochem.Biophys.Res.Commun_245_519 |
PubMedID: 9571187 |
Gene_locus related to this paper: human-PPT1 |
Title : Didemnin binds to the protein palmitoyl thioesterase responsible for infantile neuronal ceroid lipofuscinosis - Crews_1996_Proc.Natl.Acad.Sci.U.S.A_93_4316 |
Author(s) : Crews CM , Lane WS , Schreiber SL |
Ref : Proc Natl Acad Sci U S A , 93 :4316 , 1996 |
Abstract : Crews_1996_Proc.Natl.Acad.Sci.U.S.A_93_4316 |
ESTHER : Crews_1996_Proc.Natl.Acad.Sci.U.S.A_93_4316 |
PubMedSearch : Crews_1996_Proc.Natl.Acad.Sci.U.S.A_93_4316 |
PubMedID: 8633062 |
Gene_locus related to this paper: human-PPT1 |
Title : Lipid thioesters derived from acylated proteins accumulate in infantile neuronal ceroid lipofuscinosis: correction of the defect in lymphoblasts by recombinant palmitoyl-protein thioesterase - Lu_1996_Proc.Natl.Acad.Sci.U.S.A_93_10046 |
Author(s) : Lu JY , Verkruyse LA , Hofmann SL |
Ref : Proc Natl Acad Sci U S A , 93 :10046 , 1996 |
Abstract : Lu_1996_Proc.Natl.Acad.Sci.U.S.A_93_10046 |
ESTHER : Lu_1996_Proc.Natl.Acad.Sci.U.S.A_93_10046 |
PubMedSearch : Lu_1996_Proc.Natl.Acad.Sci.U.S.A_93_10046 |
PubMedID: 8816748 |
Gene_locus related to this paper: human-PPT1 |
Title : Mutations in the palmitoyl protein thioesterase gene causing infantile neuronal ceroid lipofuscinosis - Vesa_1995_Nature_376_584 |
Author(s) : Vesa J , Hellsten E , Verkruyse LA , Camp LA , Rapola J , Santavuori P , Hofmann SL , Peltonen L |
Ref : Nature , 376 :584 , 1995 |
Abstract : Vesa_1995_Nature_376_584 |
ESTHER : Vesa_1995_Nature_376_584 |
PubMedSearch : Vesa_1995_Nature_376_584 |
PubMedID: 7637805 |
Gene_locus related to this paper: human-PPT1 |