Pectinacetylesterase-Notum

Relationship

Family: Pectinacetylesterase-Notum

Block: X

Parent Family: No family

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 adenomas

Database

Interpro : IPR004963 Pectinacetylesterase\/NOTUM PAE\/NOTUM

PIRSF : No PIRSF

Pdoc : No Pdoc

Pfam : PF03283 PAE

Prints : No Print

EC Number : No EC Number

Sequences

Peptide in Fasta
Nucleotide in Fasta
Alignment with Multalin Text only
Seed alignment with MAFFT No colour
Alignment with MAFFT No colour
Dendrogram The dnd file

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)

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
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
PubMedID: 35536179
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
PubMedID: 34295610

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
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
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
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
PubMedID: 33647468
Gene_locus related to this paper: human-NOTUM

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
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
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
PubMedID: 32787107
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
PubMedID: 31534655
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
PubMedID: 30622831
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
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
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
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
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
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
PubMedID: 25115560
Gene_locus related to this paper: arath-o65713 , arath-B9DFR3 , arath-pae2 , arath-pae1

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
PubMedID: 20681952

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
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
PubMedID: 21305649
Gene_locus related to this paper: drome-q9vux3

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
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
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
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
PubMedID: 12015973
Gene_locus related to this paper: drome-q9vux3 , human-NOTUM