Pectinacetylesterase-Notum
Relationship
Comment
Pectinacetylesterase, Pectin acetylesterases from plant pathogens act as secreted enzymes to deacetylate pectins in plant cell walls. Pectins are composed mainly of galacturonic acid residues, some of which are methylated or acetylated. Pectin acetylesterases hydrolyze the ester bond linking acetyl groups to galacturonic acid. In animals Notum acts to modify heparan sulfate proteoglycans and thereby alters the extracellular gradient of Wg/Wnt protein. Kinetic and mass spectrometric analyses of human proteins show that Notum is a carboxylesterase that removes an essential palmitoleate moiety from Wnt proteins and thus constitutes the first known extracellular protein deacylase (Kakugawa et al.). Notum also deacylates octanoylated Ghrelin. Inhibitors of NOTUM showed that NOTUM could be a potential drug target for stimulating bone formation and treating osteoporosis. Loss of Apc in intestinal stem cells drives the formation of adenomas via increased WNT signalling. Apc-mutant cells are enriched for WNT antagonist Notum. Inhibition of NOTUM limited the ability of Apc-mutant cells to expand and form intestinal adenomasDatabase
Interpro : IPR004963 Pectinacetylesterase\/NOTUM PAE\/NOTUM
PIRSF : No PIRSF
Pdoc : No Pdoc
Pfam : PF03283 PAE
Prints : No Print
EC Number : No EC Number
References (25)
| Title : Virtual Screening Directly Identifies New Fragment-Sized Inhibitors of Carboxylesterase Notum with Nanomolar Activity - Steadman_2022_J.Med.Chem_65_562 |
| Author(s) : Steadman D , Atkinson BN , Zhao Y , Willis NJ , Frew S , Monaghan A , Patel C , Armstrong E , Costelloe K , Magno L , Bictash M , Jones EY , Fish PV , Svensson F |
| Ref : Journal of Medicinal Chemistry , 65 :562 , 2022 |
| Abstract : Steadman_2022_J.Med.Chem_65_562 |
| ESTHER : Steadman_2022_J.Med.Chem_65_562 |
| PubMedSearch : Steadman_2022_J.Med.Chem_65_562 |
| PubMedID: 34939789 |
| Gene_locus related to this paper: human-NOTUM |
| Title : Design of a potent, selective and brain penetrant inhibitor of Wnt-deactivating enzyme Notum by optimization of a crystallographic fragment hit - Willis_2022_J.Med.Chem_65_7212 |
| Author(s) : Willis NJ , Mahy W , Sipthorp J , Zhao Y , Woodward HL , Atkinson BN , Bayle ED , Svensson F , Frew S , Jeganathan F , Monaghan A , Benvegnu S , Jolly S , Vecchia L , Ruza RR , Kjaer S , Howell SA , Snidjers AP , Bictash M , Salinas PC , Vincent JP , Jones EY , Whiting P , Fish PV |
| Ref : Journal of Medicinal Chemistry , 65 :7212 , 2022 |
| Abstract : Willis_2022_J.Med.Chem_65_7212 |
| ESTHER : Willis_2022_J.Med.Chem_65_7212 |
| PubMedSearch : Willis_2022_J.Med.Chem_65_7212 |
| PubMedID: 35536179 |
| Gene_locus related to this paper: human-NOTUM |
| Title : Notum deletion from late-stage skeletal cells increases cortical bone formation and potentiates skeletal effects of sclerostin inhibition - Choi_2021_J.Bone.Miner.Res__ |
| Author(s) : Choi RB , Bullock WA , Hoggatt AM , Horan DJ , Pemberton EZ , Hong JM , Zhang X , He X , Robling AG |
| Ref : J Bone Miner Res , : , 2021 |
| Abstract : Choi_2021_J.Bone.Miner.Res__ |
| ESTHER : Choi_2021_J.Bone.Miner.Res__ |
| PubMedSearch : Choi_2021_J.Bone.Miner.Res__ |
| PubMedID: 34223673 |
| Gene_locus related to this paper: human-NOTUM , mouse-notum |
| Title : NOTUM from Apc-mutant cells biases clonal competition to initiate cancer - Flanagan_2021_Nature__ |
| Author(s) : Flanagan DJ , Pentinmikko N , Luopajarvi K , Willis NJ , Gilroy K , Raven AP , McGarry L , Englund JI , Webb AT , Scharaw S , Nasreddin N , Hodder MC , Ridgway RA , Minnee E , Sphyris N , Gilchrist E , Najumudeen AK , Romagnolo B , Perret C , Williams AC , Clevers H , Nummela P , Lahde M , Alitalo K , Hietakangas V , Hedley A , Clark W , Nixon C , Kirschner K , Jones EY , Ristimaki A , Leedham SJ , Fish PV , Vincent JP , Katajisto P , Sansom OJ |
| Ref : Nature , : , 2021 |
| Abstract : Flanagan_2021_Nature__ |
| ESTHER : Flanagan_2021_Nature__ |
| PubMedSearch : Flanagan_2021_Nature__ |
| PubMedID: 34079124 |
| Gene_locus related to this paper: human-NOTUM |
| Title : Small-molecule inhibitors of carboxylesterase Notum - Zhao_2021_Future.Med.Chem__ |
| Author(s) : Zhao Y , Jolly S , Benvegnu S , Jones EY , Fish PV |
| Ref : Future Med Chem , : , 2021 |
| Abstract : Zhao_2021_Future.Med.Chem__ |
| ESTHER : Zhao_2021_Future.Med.Chem__ |
| PubMedSearch : Zhao_2021_Future.Med.Chem__ |
| PubMedID: 33882714 |
| Gene_locus related to this paper: human-NOTUM |
| Title : Notum Deacylates Octanoylated Ghrelin - Zhao_2021_Mol.Metab__101201 |
| Author(s) : Zhao Y , Schuhmacher LN , Roberts M , Kakugawa S , Bineva-Todd G , Howell S , O'Reilly N , Perret C , Snijders AP , Vincent JP , Jones EY |
| Ref : Mol Metab , :101201 , 2021 |
| Abstract : Zhao_2021_Mol.Metab__101201 |
| ESTHER : Zhao_2021_Mol.Metab__101201 |
| PubMedSearch : Zhao_2021_Mol.Metab__101201 |
| PubMedID: 33647468 |
| Gene_locus related to this paper: human-NOTUM |
| Title : Bioinformatics analysis of PAE family in Populus trichocarpa and responsiveness to carbon and nitrogen treatment - Xu_2021_3.Biotech_11_370 |
| Author(s) : Xu C , Zhang S , Suo J , Chang R , Xu X , Xu Z , Yang C , Qu C , Liu G |
| Ref : 3 Biotech , 11 :370 , 2021 |
| Abstract : Xu_2021_3.Biotech_11_370 |
| ESTHER : Xu_2021_3.Biotech_11_370 |
| PubMedSearch : Xu_2021_3.Biotech_11_370 |
| PubMedID: 34295610 |
| Title : 5-Phenyl-1,3,4-oxadiazol-2(3H)-ones Are Potent Inhibitors of Notum Carboxylesterase Activity Identified by the Optimization of a Crystallographic Fragment Screening Hit - Mahy_2020_J.Med.Chem_63_12942 |
| Author(s) : Mahy W , Willis NJ , Zhao Y , Woodward HL , Svensson F , Sipthorp J , Vecchia L , Ruza RR , Hillier J , Kjr S , Frew S , Monaghan A , Bictash M , Salinas PC , Whiting P , Vincent JP , Jones EY , Fish PV |
| Ref : Journal of Medicinal Chemistry , 63 :12942 , 2020 |
| Abstract : Mahy_2020_J.Med.Chem_63_12942 |
| ESTHER : Mahy_2020_J.Med.Chem_63_12942 |
| PubMedSearch : Mahy_2020_J.Med.Chem_63_12942 |
| PubMedID: 33124429 |
| Gene_locus related to this paper: human-NOTUM |
| Title : Caffeine inhibits Notum activity by binding at the catalytic pocket - Zhao_2020_Commun.Biol_3_555 |
| Author(s) : Zhao Y , Ren J , Hillier J , Lu W , Jones EY |
| Ref : Commun Biol , 3 :555 , 2020 |
| Abstract : Zhao_2020_Commun.Biol_3_555 |
| ESTHER : Zhao_2020_Commun.Biol_3_555 |
| PubMedSearch : Zhao_2020_Commun.Biol_3_555 |
| PubMedID: 33033363 |
| Gene_locus related to this paper: human-NOTUM |
| Title : Screening of a Custom-Designed Acid Fragment Library Identifies 1-Phenylpyrroles and 1-Phenylpyrrolidines as Inhibitors of Notum Carboxylesterase Activity - Mahy_2020_J.Med.Chem_63_9464 |
| Author(s) : Mahy W , Patel M , Steadman D , Woodward HL , Atkinson BN , Svensson F , Willis NJ , Flint A , Papatheodorou D , Zhao Y , Vecchia L , Ruza RR , Hillier J , Frew S , Monaghan A , Costa A , Bictash M , Walter MW , Jones EY , Fish PV |
| Ref : Journal of Medicinal Chemistry , 63 :9464 , 2020 |
| Abstract : Mahy_2020_J.Med.Chem_63_9464 |
| ESTHER : Mahy_2020_J.Med.Chem_63_9464 |
| PubMedSearch : Mahy_2020_J.Med.Chem_63_9464 |
| PubMedID: 32787107 |
| Gene_locus related to this paper: human-NOTUM |
| Title : NOTUM inhibition increases endocortical bone formation and bone strength - Brommage_2019_Bone.Res_7_2 |
| Author(s) : Brommage R , Liu J , Vogel P , Mseeh F , Thompson AY , Potter DG , Shadoan MK , Hansen GM , Jeter-Jones S , Cui J , Bright D , Bardenhagen JP , Doree DD , Moverare-Skrtic S , Nilsson KH , Henning P , Lerner UH , Ohlsson C , Sands AT , Tarver JE , Powell DR , Zambrowicz B , Liu Q |
| Ref : Bone Res , 7 :2 , 2019 |
| Abstract : Brommage_2019_Bone.Res_7_2 |
| ESTHER : Brommage_2019_Bone.Res_7_2 |
| PubMedSearch : Brommage_2019_Bone.Res_7_2 |
| PubMedID: 30622831 |
| Gene_locus related to this paper: human-NOTUM |
| Title : Discovery of 2-phenoxyacetamides as inhibitors of the Wnt-depalmitoleating enzyme NOTUM from an X-ray fragment screen - Atkinson_2019_Medchemcomm_10_1361 |
| Author(s) : Atkinson BN , Steadman D , Zhao YG , Sipthorp J , Vecchia L , Ruza RR , Jeganathan F , Lines G , Frew S , Monaghan A , Kjaer S , Bictash M , Jones Y , Fish PV , Zhao Y , Jones EY |
| Ref : Medchemcomm , 10 :1361 , 2019 |
| Abstract : Atkinson_2019_Medchemcomm_10_1361 |
| ESTHER : Atkinson_2019_Medchemcomm_10_1361 |
| PubMedSearch : Atkinson_2019_Medchemcomm_10_1361 |
| PubMedID: 31534655 |
| Gene_locus related to this paper: human-NOTUM |
| Title : Plant pectin acetylesterase structure and function: new insights from bioinformatic analysis - Philippe_2017_BMC.Genomics_18_456 |
| Author(s) : Philippe F , Pelloux J , Rayon C |
| Ref : BMC Genomics , 18 :456 , 2017 |
| Abstract : Philippe_2017_BMC.Genomics_18_456 |
| ESTHER : Philippe_2017_BMC.Genomics_18_456 |
| PubMedSearch : Philippe_2017_BMC.Genomics_18_456 |
| PubMedID: 28595570 |
| Gene_locus related to this paper: arath-o65713 , arath-o80731 , arath-q8lae9 , arath-Q84JS1 , arath-Q9SFF6 , arath-q9sr22 , arath-q9sr23 , arath-q66gm8 , arath-f4jt64 , arath-B9DFR3 , arath-pae2 , arath-pae1 |
| Title : Generation of Mice with Hepatocyte-Specific Conditional Deletion of Notum - Canal_2016_PLoS.One_11_e0150997 |
| Author(s) : Canal F , Charawi S , Grimber G , Houbron C , Drouet V , Colnot S , Terris B , Cavard C , Perret C |
| Ref : PLoS ONE , 11 :e0150997 , 2016 |
| Abstract : Canal_2016_PLoS.One_11_e0150997 |
| ESTHER : Canal_2016_PLoS.One_11_e0150997 |
| PubMedSearch : Canal_2016_PLoS.One_11_e0150997 |
| PubMedID: 26974334 |
| Gene_locus related to this paper: mouse-notum |
| Title : Stimulation of cortical bone formation with thienopyrimidine based inhibitors of Notum Pectinacetylesterase - Tarver_2016_Bioorg.Med.Chem.Lett_26_1525 |
| Author(s) : Tarver JE, Jr. , Pabba PK , Barbosa J , Han Q , Gardyan MW , Brommage R , Thompson AY , Schmidt JM , Wilson AG , He W , Lombardo VK , Carson KG , Wilson AGE |
| Ref : Bioorganic & Medicinal Chemistry Lett , 26 :1525 , 2016 |
| Abstract : Tarver_2016_Bioorg.Med.Chem.Lett_26_1525 |
| ESTHER : Tarver_2016_Bioorg.Med.Chem.Lett_26_1525 |
| PubMedSearch : Tarver_2016_Bioorg.Med.Chem.Lett_26_1525 |
| PubMedID: 26897593 |
| Gene_locus related to this paper: human-NOTUM |
| Title : Notum Is Required for Neural and Head Induction via Wnt Deacylation, Oxidation, and Inactivation - Zhang_2015_Dev.Cell_32_719 |
| Author(s) : Zhang X , Cheong SM , Amado NG , Reis AH , MacDonald BT , Zebisch M , Jones EY , Abreu JG , He X |
| Ref : Dev Cell , 32 :719 , 2015 |
| Abstract : Zhang_2015_Dev.Cell_32_719 |
| ESTHER : Zhang_2015_Dev.Cell_32_719 |
| PubMedSearch : Zhang_2015_Dev.Cell_32_719 |
| PubMedID: 25771893 |
| Title : Notum deacylates Wnt proteins to suppress signalling activity - Kakugawa_2015_Nature_519_187 |
| Author(s) : Kakugawa S , Langton PF , Zebisch M , Howell SA , Chang TH , Liu Y , Feizi T , Bineva G , O'Reilly N , Snijders AP , Jones EY , Vincent JP |
| Ref : Nature , 519 :187 , 2015 |
| Abstract : Kakugawa_2015_Nature_519_187 |
| ESTHER : Kakugawa_2015_Nature_519_187 |
| PubMedSearch : Kakugawa_2015_Nature_519_187 |
| PubMedID: 25731175 |
| Gene_locus related to this paper: drome-q9vux3 , human-NOTUM |
| Title : Identification and functional characterization of the distinct plant pectin esterases PAE8 and PAE9 and their deletion mutants - de Souza_2014_Planta_240_1123 |
| Author(s) : de Souza A , Hull PA , Gille S , Pauly M |
| Ref : Planta , 240 :1123 , 2014 |
| Abstract : de Souza_2014_Planta_240_1123 |
| ESTHER : de Souza_2014_Planta_240_1123 |
| PubMedSearch : de Souza_2014_Planta_240_1123 |
| PubMedID: 25115560 |
| Gene_locus related to this paper: arath-o65713 , arath-B9DFR3 , arath-pae2 , arath-pae1 |
| Title : Polarized notum activation at wounds inhibits Wnt function to promote planarian head regeneration - Petersen_2011_Science_332_852 |
| Author(s) : Petersen CP , Reddien PW |
| Ref : Science , 332 :852 , 2011 |
| Abstract : Petersen_2011_Science_332_852 |
| ESTHER : Petersen_2011_Science_332_852 |
| PubMedSearch : Petersen_2011_Science_332_852 |
| PubMedID: 21566195 |
| Gene_locus related to this paper: schmd-f8u830 |
| Title : Sulfated is a negative feedback regulator of wingless in Drosophila - You_2011_Dev.Dyn_240_640 |
| Author(s) : You J , Belenkaya T , Lin X |
| Ref : Developmental Dynamics , 240 :640 , 2011 |
| Abstract : You_2011_Dev.Dyn_240_640 |
| ESTHER : You_2011_Dev.Dyn_240_640 |
| PubMedSearch : You_2011_Dev.Dyn_240_640 |
| PubMedID: 21305649 |
| Gene_locus related to this paper: drome-q9vux3 |
| Title : Glypican-1 facilitates prion conversion in lipid rafts - Hooper_2011_J.Neurochem_116_721 |
| Author(s) : Hooper NM |
| Ref : Journal of Neurochemistry , 116 :721 , 2011 |
| Abstract : Hooper_2011_J.Neurochem_116_721 |
| ESTHER : Hooper_2011_J.Neurochem_116_721 |
| PubMedSearch : Hooper_2011_J.Neurochem_116_721 |
| PubMedID: 20681952 |
| Title : Mammalian Notum induces the release of glypicans and other GPI-anchored proteins from the cell surface - Traister_2008_Biochem.J_410_503 |
| Author(s) : Traister A , Shi W , Filmus J |
| Ref : Biochemical Journal , 410 :503 , 2008 |
| Abstract : Traister_2008_Biochem.J_410_503 |
| ESTHER : Traister_2008_Biochem.J_410_503 |
| PubMedSearch : Traister_2008_Biochem.J_410_503 |
| PubMedID: 17967162 |
| Title : Opposing activities of Dally-like glypican at high and low levels of Wingless morphogen activity - Kreuger_2004_Dev.Cell_7_503 |
| Author(s) : Kreuger J , Perez L , Giraldez AJ , Cohen SM |
| Ref : Dev Cell , 7 :503 , 2004 |
| Abstract : Kreuger_2004_Dev.Cell_7_503 |
| ESTHER : Kreuger_2004_Dev.Cell_7_503 |
| PubMedSearch : Kreuger_2004_Dev.Cell_7_503 |
| PubMedID: 15469839 |
| Title : Wingful, an extracellular feedback inhibitor of Wingless - Gerlitz_2002_Genes.Dev_16_1055 |
| Author(s) : Gerlitz O , Basler K |
| Ref : Genes Dev , 16 :1055 , 2002 |
| Abstract : Gerlitz_2002_Genes.Dev_16_1055 |
| ESTHER : Gerlitz_2002_Genes.Dev_16_1055 |
| PubMedSearch : Gerlitz_2002_Genes.Dev_16_1055 |
| PubMedID: 12000788 |
| Gene_locus related to this paper: drome-q9vux3 |
| Title : HSPG modification by the secreted enzyme Notum shapes the Wingless morphogen gradient - Giraldez_2002_Dev.Cell_2_667 |
| Author(s) : Giraldez AJ , Copley RR , Cohen SM |
| Ref : Dev Cell , 2 :667 , 2002 |
| Abstract : Giraldez_2002_Dev.Cell_2_667 |
| ESTHER : Giraldez_2002_Dev.Cell_2_667 |
| PubMedSearch : Giraldez_2002_Dev.Cell_2_667 |
| PubMedID: 12015973 |
| Gene_locus related to this paper: drome-q9vux3 , human-NOTUM |
Structures (143)
Genes Proteins in Pectinacetylesterase-Notum family (695)
Fragments of genes in Pectinacetylesterase-Notum family (201)
Structures in Pectinacetylesterase-Notum family (143)Substrates in Pectinacetylesterase-Notum family (7)
Inhibitors in Pectinacetylesterase-Notum family (137)