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Family Report for: Pectinacetylesterase-Notum

Pectinacetylesterase-Notum



Relationship
Block X
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
Sequences
Interpro
|
IPR004963 (Pectinacetylesterase/NOTUM PAE/NOTUM)
PIRSF
|
Pdoc
|
PFam
|
PF03283 (PAE)
Prints
|
Prosite
|
no EC number



Peptide in
|Fasta
Nucleotide in
|Fasta
Alignment with Multalin
|Text only/graphic display
Seed alignment with MAFFT
|No colour/coloured with Mview
Alignment with MAFFT
|No colour/coloured with Mview
Dendrogram
|Graphical display, obtained with the dnd file produced by Clustalw

References
22 more
    Title: Virtual Screening Directly Identifies New Fragment-Sized Inhibitors of Carboxylesterase Notum with Nanomolar Activity
    Steadman D, Atkinson BN, Zhao Y, Willis NJ, Frew S, Monaghan A, Patel C, Armstrong E, Costelloe K and Svensson F <4 more author(s)>
    Ref: Journal of Medicinal Chemistry, 65:562, 2022 : PubMed

            

    Title: Design of a potent, selective and brain penetrant inhibitor of Wnt-deactivating enzyme Notum by optimization of a crystallographic fragment hit
    Willis NJ, Mahy W, Sipthorp J, Zhao Y, Woodward HL, Atkinson BN, Bayle ED, Svensson F, Frew S and Fish PV <14 more author(s)>
    Ref: Journal of Medicinal Chemistry, 65:7212, 2022 : PubMed

            

    Title: Bioinformatics analysis of PAE family in Populus trichocarpa and responsiveness to carbon and nitrogen treatment
    Xu C, Zhang S, Suo J, Chang R, Xu X, Xu Z, Yang C, Qu C, Liu G
    Ref: 3 Biotech, 11:370, 2021 : PubMed

            

Other Papers


No structure scheme yet for this family

Structures in Pectinacetylesterase-Notum family (143)

Genes Proteins in Pectinacetylesterase-Notum family (695)

Fragments of genes in Pectinacetylesterase-Notum family (201)

Substrates of some enzymes in the Pectinacetylesterase-Notum family (7)

Inhibitors of some enzymes in the Pectinacetylesterase-Notum family (137)



Send your questions or comments to :
Mail to: Nicolas Lenfant, Thierry Hotelier, Yves Bourne, Pascale Marchot and Arnaud Chatonnet.
Please cite: Lenfant 2013 Nucleic.Acids.Res. or Marchot Chatonnet 2012 Prot.Pept Lett.
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