human-LYPLA1
Homo sapiens (Human) lysophospholipase I (LYPLA1) APT1, acyl-protein thioesterase 1 S-depalmitoylase
Comment
Increasing brain palmitoylation rescues behavior and neuropathology in Huntington disease mice. Inhibition of APT-1 restaures the axonal transport. Under development for treatment of Hutington disease. || Previously characterized as lysophospholipase I, but has several hundred-fold higher activity as a protein thioesterase. Acyl protein thioesterase apt1, which catalyzes depalmitoylation of Galpha proteins and Ras. S-depalmitoylase found both in cytoplasm and mitochondria || . A shorter form exists as a splice variant AF077199 nuc 4679011 pep 4679012 || . Q9UQF9 probable isoform of same gene
Relationship
Family : LYsophospholipase_carboxylesterase
Block : X
Position in NCBI Life Tree : Homo sapiens
(Below N is a link to NCBI taxonomic web page and E link to ESTHER at designed phylum.)
> cellular organisms N E > Eukaryota N E > Opisthokonta N E > Metazoa N E > Eumetazoa N E > Bilateria N E > Deuterostomia N E > Chordata N E > Craniata N E > Vertebrata N E > Gnathostomata N E > Teleostomi N E > Euteleostomi N E > Sarcopterygii N E > Dipnotetrapodomorpha N E > Tetrapoda N E > Amniota N E > Mammalia N E > Theria N E > Eutheria N E > Boreoeutheria N E > Euarchontoglires N E > Primates N E > Haplorrhini N E > Simiiformes N E > Catarrhini N E > Hominoidea N E > Hominidae N E > Homininae N E > Homo N E > Homo sapiens N EMolecular evidence
No mutation
1FJ2 - human acyl protein thioesterase 1 at 1.5 A resolution
5SYM - Cocrystal structure of the human acyl protein thioesterase 1 with an isoform-selective inhibitor, ML348
6QGN - Crystal structure of human acyl protein thioesterase APT1 bound to 2-Bromopalmitate
6QGO - Crystal structure of human acyl protein thioesterase APT1 S119A mutant bound to palmitic acid
6QGQ - Crystal structure of human acyl protein thioesterase APT1 C2S mutant bound to palmitic acid
6QGS - Crystal structure of human acyl protein thioesterase APT1 bound to palmitic acid
No kinetic
No disease
Sequence
Peptide
MCGNNMSTPL PAIVPAARKA TAAVIFLHGL GDTGHGWAEA FAGIRSSHIK YICPHAPVRP VTLNMNVAMP SWFDIIGLSP DSQEDESGIK QAAENIKALI DQEVKNGIPS NRIILGGFSQ GGALSLYTAL TTQQKLAGVT ALSCWLPLRA SFPQGPIGGA NRDISILQCH GDCDPLVPLM FGSLTVEKLK TLVNPANVTF KTYEGMMHSS CQQEMMDVKQ FIDKLLPPID
References (23)
| Title : Identification of Acyl-Protein Thioesterase-1 as a Polysorbate-degrading Host Cell Protein in a Monoclonal Antibody Formulation Using Activity-based Protein Profiling - Sprager_2024_J.Pharm.Sci__ |
| Author(s) : Sprager E , Moller J , Lin Y , Reisinger V , Bratkovic T , Lunder M , Vasl J , Krajnc A |
| Ref : J Pharm Sci , : , 2024 |
| Abstract : |
| PubMedSearch : Sprager_2024_J.Pharm.Sci__ |
| PubMedID: 38772451 |
| Gene_locus related to this paper: human-LYPLA1 |
| Title : A conserved but structurally divergent loop in acyl protein thioesterase 1 regulates its catalytic activity, ligand binding, and folded stability - Harris_2024_Proteins__ |
| Author(s) : Harris WT, 3rd , Altieri I , Gieck I , Johnson RJ |
| Ref : Proteins , : , 2024 |
| Abstract : |
| PubMedSearch : Harris_2024_Proteins__ |
| PubMedID: 38179877 |
| Gene_locus related to this paper: human-LYPLA1 |
| Title : Palmitoyltransferase DHHC9 and acyl protein thioesterase APT1 modulate renal fibrosis through regulating beta-catenin palmitoylation - Gu_2023_Nat.Commun_14_6682 |
| Author(s) : Gu M , Jiang H , Tan M , Yu L , Xu N , Li Y , Wu H , Hou Q , Dai C |
| Ref : Nat Commun , 14 :6682 , 2023 |
| Abstract : |
| PubMedSearch : Gu_2023_Nat.Commun_14_6682 |
| PubMedID: 37865665 |
| Gene_locus related to this paper: human-LYPLA1 |
| Title : Hepatic palmitoyl-proteomes and acyl-protein thioesterase protein proximity networks link lipid modification and mitochondria - Speck_2023_Cell.Rep_42_113389 |
| Author(s) : Speck SL , Bhatt DP , Zhang Q , Adak S , Yin L , Dong G , Feng C , Zhang W , Ben Major M , Wei X , Semenkovich CF |
| Ref : Cell Rep , 42 :113389 , 2023 |
| Abstract : |
| PubMedSearch : Speck_2023_Cell.Rep_42_113389 |
| PubMedID: 37925639 |
| Gene_locus related to this paper: human-LYPLA1 , human-LYPLA2 , mouse-lypla1 , mouse-lypla2 |
| Title : APT1-Mediated Depalmitoylation Regulates Hippocampal Synaptic Plasticity - Shen_2022_J.Neurosci_42_2662 |
| Author(s) : Shen ZC , Xia ZX , Liu JM , Zheng JY , Luo YF , Yang H , Li MD , Cao T , Liu HP , Jin GL , Huang HH , Yu CX , Zhou J |
| Ref : Journal of Neuroscience , 42 :2662 , 2022 |
| Abstract : |
| PubMedSearch : Shen_2022_J.Neurosci_42_2662 |
| PubMedID: 35165175 |
| Gene_locus related to this paper: human-LYPLA1 |
| Title : Increasing brain palmitoylation rescues behavior and neuropathology in Huntington disease mice - Virlogeux_2021_Sci.Adv_7_eabb0799 |
| Author(s) : Virlogeux A , Scaramuzzino C , Lenoir S , Carpentier R , Louessard M , Genoux A , Lino P , Hinckelmann MV , Perrier AL , Humbert S , Saudou F |
| Ref : Sci Adv , 7 : , 2021 |
| Abstract : |
| PubMedSearch : Virlogeux_2021_Sci.Adv_7_eabb0799 |
| PubMedID: 33789888 |
| Gene_locus related to this paper: human-LYPLA1 |
| Title : In a mouse model of INCL reduced S-palmitoylation of cytosolic thioesterase APT1 contributes to microglia proliferation and neuroinflammation - Sadhukhan_2021_J.Inherit.Metab.Dis_44_1051 |
| Author(s) : Sadhukhan T , Bagh MB , Appu AP , Mondal A , Zhang W , Liu A , Mukherjee AB |
| Ref : J Inherit Metab Dis , 44 :1051 , 2021 |
| Abstract : |
| PubMedSearch : Sadhukhan_2021_J.Inherit.Metab.Dis_44_1051 |
| PubMedID: 33739454 |
| Gene_locus related to this paper: human-LYPLA1 , mouse-lypla1 |
| Title : Palmitoylated acyl protein thioesterase APT2 deforms membranes to extract substrate acyl chains - Abrami_2021_Nat.Chem.Biol_17_438 |
| Author(s) : Abrami L , Audagnotto M , Ho S , Marcaida MJ , Mesquita FS , Anwar MU , Sandoz PA , Fonti G , Pojer F , Dal Peraro M , van der Goot FG |
| Ref : Nat Chemical Biology , 17 :438 , 2021 |
| Abstract : |
| PubMedSearch : Abrami_2021_Nat.Chem.Biol_17_438 |
| PubMedID: 33707782 |
| Gene_locus related to this paper: human-LYPLA1 , human-LYPLA2 |
| Title : Inhibition of cell proliferation and migration in nonsmall cell lung cancer cells through the suppression of LYPLA1 - Mohammed_2019_Oncol.Rep_41_973 |
| Author(s) : Mohammed A , Zhang C , Zhang S , Shen Q , Li J , Tang Z , Liu H |
| Ref : Oncol Rep , 41 :973 , 2019 |
| Abstract : |
| PubMedSearch : Mohammed_2019_Oncol.Rep_41_973 |
| PubMedID: 30431103 |
| Gene_locus related to this paper: human-LYPLA1 |
| Title : Wnt5a signaling induced phosphorylation increases APT1 activity and promotes melanoma metastatic behavior - Sadeghi_2018_Elife_7_ |
| Author(s) : Sadeghi RS , Kulej K , Kathayat RS , Garcia BA , Dickinson BC , Brady DC , Witze ES |
| Ref : Elife , 7 : , 2018 |
| Abstract : |
| PubMedSearch : Sadeghi_2018_Elife_7_ |
| PubMedID: 29648538 |
| Gene_locus related to this paper: human-LYPLA1 , mouse-lypla1 |
| Title : Active and dynamic mitochondrial S-depalmitoylation revealed by targeted fluorescent probes - Kathayat_2018_Nat.Commun_9_334 |
| Author(s) : Kathayat RS , Cao Y , Elvira PD , Sandoz PA , Zaballa ME , Springer MZ , Drake LE , Macleod KF , van der Goot FG , Dickinson BC |
| Ref : Nat Commun , 9 :334 , 2018 |
| Abstract : |
| PubMedSearch : Kathayat_2018_Nat.Commun_9_334 |
| PubMedID: 29362370 |
| Gene_locus related to this paper: human-LYPLA1 |
| Title : Acyl protein thioesterase 1 and 2 (APT-1, APT-2) inhibitors palmostatin B, ML348 and ML349 have different effects on NRAS mutant melanoma cells - Vujic_2016_Oncotarget_7_7297 |
| Author(s) : Vujic I , Sanlorenzo M , Esteve-Puig R , Vujic M , Kwong A , Tsumura A , Murphy R , Moy A , Posch C , Monshi B , Rappersberger K , Ortiz-Urda S |
| Ref : Oncotarget , 7 :7297 , 2016 |
| Abstract : |
| PubMedSearch : Vujic_2016_Oncotarget_7_7297 |
| PubMedID: 26771141 |
| Gene_locus related to this paper: human-LYPLA1 , human-LYPLA2 |
| Title : Molecular Mechanism for Isoform-Selective Inhibition of Acyl Protein Thioesterases 1 and 2 (APT1 and APT2) - Won_2016_ACS.Chem.Biol_11_3374 |
| Author(s) : Won SJ , Davda D , Labby KJ , Hwang SY , Pricer R , Majmudar JD , Armacost KA , Rodriguez LA , Rodriguez CL , Chong FS , Torossian KA , Palakurthi J , Hur ES , Meagher JL , Brooks CL, 3rd , Stuckey JA , Martin BR |
| Ref : ACS Chemical Biology , 11 :3374 , 2016 |
| Abstract : |
| PubMedSearch : Won_2016_ACS.Chem.Biol_11_3374 |
| PubMedID: 27748579 |
| Gene_locus related to this paper: human-LYPLA1 , human-LYPLA2 |
| Title : Acyl protein thioesterase inhibitors as probes of dynamic S-palmitoylation - Davda_2014_Medchemcomm_5_268 |
| Author(s) : Davda D , Martin BR |
| Ref : Medchemcomm , 5 :268 , 2014 |
| Abstract : |
| PubMedSearch : Davda_2014_Medchemcomm_5_268 |
| PubMedID: 25558349 |
| Gene_locus related to this paper: human-LYPLA1 |
| Title : Distinct acyl protein transferases and thioesterases control surface expression of calcium-activated potassium channels - Tian_2012_J.Biol.Chem_287_14718 |
| Author(s) : Tian L , McClafferty H , Knaus HG , Ruth P , Shipston MJ |
| Ref : Journal of Biological Chemistry , 287 :14718 , 2012 |
| Abstract : |
| PubMedSearch : Tian_2012_J.Biol.Chem_287_14718 |
| PubMedID: 22399288 |
| Gene_locus related to this paper: human-LYPLA1 |
| Title : Identification of acyl protein thioesterases 1 and 2 as the cellular targets of the Ras-signaling modulators palmostatin B and M - Rusch_2011_Angew.Chem.Int.Ed.Engl_50_9838 |
| Author(s) : Rusch M , Zimmermann TJ , Burger M , Dekker FJ , Gormer K , Triola G , Brockmeyer A , Janning P , Bottcher T , Sieber SA , Vetter IR , Hedberg C , Waldmann H |
| Ref : Angew Chem Int Ed Engl , 50 :9838 , 2011 |
| Abstract : |
| PubMedSearch : Rusch_2011_Angew.Chem.Int.Ed.Engl_50_9838 |
| PubMedID: 21905186 |
| Gene_locus related to this paper: human-LYPLA1 , human-LYPLA2 |
| Title : Small-molecule inhibition of APT1 affects Ras localization and signaling - Dekker_2010_Nat.Chem.Biol_6_449 |
| Author(s) : Dekker FJ , Rocks O , Vartak N , Menninger S , Hedberg C , Balamurugan R , Wetzel S , Renner S , Gerauer M , Scholermann B , Rusch M , Kramer JW , Rauh D , Coates GW , Brunsveld L , Bastiaens PI , Waldmann H |
| Ref : Nat Chemical Biology , 6 :449 , 2010 |
| Abstract : |
| PubMedSearch : Dekker_2010_Nat.Chem.Biol_6_449 |
| PubMedID: 20418879 |
| Gene_locus related to this paper: human-LYPLA1 |
| Title : A functional screen implicates microRNA-138-dependent regulation of the depalmitoylation enzyme APT1 in dendritic spine morphogenesis - Siegel_2009_Nat.Cell.Biol_11_705 |
| Author(s) : Siegel G , Obernosterer G , Fiore R , Oehmen M , Bicker S , Christensen M , Khudayberdiev S , Leuschner PF , Busch CJ , Kane C , Hubel K , Dekker F , Hedberg C , Rengarajan B , Drepper C , Waldmann H , Kauppinen S , Greenberg ME , Draguhn A , Rehmsmeier M , Martinez J , Schratt GM |
| Ref : Nat Cell Biol , 11 :705 , 2009 |
| Abstract : |
| PubMedSearch : Siegel_2009_Nat.Cell.Biol_11_705 |
| PubMedID: 19465924 |
| Gene_locus related to this paper: human-LYPLA1 |
| Title : Protein acyl thioesterases (Review) - Zeidman_2009_Mol.Membr.Biol_26_32 |
| Author(s) : Zeidman R , Jackson CS , Magee AI |
| Ref : Mol Membr Biol , 26 :32 , 2009 |
| Abstract : |
| PubMedSearch : Zeidman_2009_Mol.Membr.Biol_26_32 |
| PubMedID: 19115143 |
| Gene_locus related to this paper: human-LYPLA1 , human-PPT1 |
| Title : Crystal structure of the human acyl protein thioesterase I from a single X-ray data set to 1.5 A - Devedjiev_2000_Structure_8_1137 |
| Author(s) : Devedjiev Y , Dauter Z , Kuznetsov SR , Jones TL , Derewenda ZS |
| Ref : Structure , 8 :1137 , 2000 |
| Abstract : |
| PubMedSearch : Devedjiev_2000_Structure_8_1137 |
| PubMedID: 11080636 |
| Gene_locus related to this paper: human-LYPLA1 |
| Title : Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem\/progenitor cells - Zhang_2000_Genome.Res_10_1546 |
| Author(s) : Zhang QH , Ye M , Wu XY , Ren SX , Zhao M , Zhao CJ , Fu G , Shen Y , Fan HY , Lu G , Zhong M , Xu XR , Han ZG , Zhang JW , Tao J , Huang QH , Zhou J , Hu GX , Gu J , Chen SJ , Chen Z |
| Ref : Genome Res , 10 :1546 , 2000 |
| Abstract : |
| PubMedSearch : Zhang_2000_Genome.Res_10_1546 |
| PubMedID: 11042152 |
| Gene_locus related to this paper: human-LYPLA1 |
| Title : A specific human lysophospholipase: cDNA cloning, tissue distribution and kinetic characterization - Wang_1999_Biochim.Biophys.Acta_1437_157 |
| Author(s) : Wang A , Yang HC , Friedman P , Johnson CA , Dennis EA |
| Ref : Biochimica & Biophysica Acta , 1437 :157 , 1999 |
| Abstract : |
| PubMedSearch : Wang_1999_Biochim.Biophys.Acta_1437_157 |
| PubMedID: 10064899 |
| Gene_locus related to this paper: human-LYPLA1 |
| Title : A cytoplasmic acyl-protein thioesterase that removes palmitate from G protein alpha subunits and p21(RAS) - Duncan_1998_J.Biol.Chem_273_15830 |
| Author(s) : Duncan JA , Gilman AG |
| Ref : Journal of Biological Chemistry , 273 :15830 , 1998 |
| Abstract : |
| PubMedSearch : Duncan_1998_J.Biol.Chem_273_15830 |
| PubMedID: 9624183 |
| Gene_locus related to this paper: human-LYPLA1 , ratno-lypla1a |