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Gene_locus Report for: human-NOTUM

Homo sapiens (Human) Protein notum homolog

Comment
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


Relationship
Family|Pectinacetylesterase-Notum
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 E


Molecular evidence
Database
No mutation
127 structures (e.g. : 4UYU, 4UYW, 4UYZ... more)
No kinetic





6 substrates (e.g. : Myristic-acid, OPTS, Octanoyl-ghrelin... more)
121 inhibitors (e.g. : (4-fluoroanilino)thiourea, (Isoquinolin-1-ylsulfanyl)-acetic-acid, 1-Naphthalenepentanoic-acid... more)
>3 Genbank links 1 more: BC036872, BC060882, AB062438
3 UniProt : Q6P988, C9JYG8, K7EIG3
>3 Structure links 124 more: 7PJR, 7QVZ, 7PK3
3 UniProt : Q6P988, C9JYG8, K7EIG3
3 Interpro : Q6P988, C9JYG8, K7EIG3
3 Prodom : Q6P988, C9JYG8, K7EIG3
3 Pfam : Q6P988, C9JYG8, K7EIG3
3 PIRSF : Q6P988, C9JYG8, K7EIG3
3 SUPERFAM : Q6P988, C9JYG8, K7EIG3
1 EntrezGene : 147111
1 SNP : 147111
1 UniGene : 106137
1 HUGO HGNC : 27106
1 OMIM : 609847
1 Ensembl : ENSG00000185269
Sequence
Graphical view for this peptide sequence: human-NOTUM
Colored MSA for Pectinacetylesterase-Notum (raw)
MGRGVRVLLLLSLLHCAGGSEGRKTWRRRGQQPPPPPRTEAAPAAGQPVE
SFPLDFTAVEGNMDSFMAQVKSLAQSLYPCSAQQLNEDLRLHLLLNTSVT
CNDGSPAGYYLKESRGSRRWLLFLEGGWYCFNRENCDSRYDTMRRLMSSR
DWPRTRTGTGILSSQPEENPYWWNANMVFIPYCSSDVWSGASSKSEKNEY
AFMGALIIQEVVRELLGRGLSGAKVLLLAGSSAGGTGVLLNVDRVAEQLE
KLGYPAIQVRGLADSGWFLDNKQYRHTDCVDTITCAPTEAIRRGIRYWNG
VVPERCRRQFQEGEEWNCFFGYKVYPTLRCPVFVVQWLFDEAQLTVDNVH
LTGQPVQEGLRLYIQNLGRELRHTLKDVPASFAPACLSHEIIIRSHWTDV
QVKGTSLPRALHCWDRSLHDSHKASKTPLKGCPVHLVDSCPWPHCNPSCP
TVRDQFTGQEMNVAQFLMHMGFDMQTVAQPQGLEPSELLGMLSNGS
Legend This sequence has been compared to family alignement (MSA)
red => minority aminoacid
blue => majority aminoacid
color intensity => conservation rate
title => sequence position(MSA position)aminoacid rate
Catalytic site
Catalytic site in the MSA

MGRGVRVLLLLSLLHCAGGSEGRKTWRRRGQQPPPPPRTEAAPAAGQPVE
SFPLDFTAVEGNMDSFMAQVKSLAQSLYPCSAQQLNEDLRLHLLLNTSVT
CNDGSPAGYYLKESRGSRRWLLFLEGGWYCFNRENCDSRYDTMRRLMSSR
DWPRTRTGTGILSSQPEENPYWWNANMVFIPYCSSDVWSGASSKSEKNEY
AFMGALIIQEVVRELLGRGLSGAKVLLLAGSSAGGTGVLLNVDRVAEQLE
KLGYPAIQVRGLADSGWFLDNKQYRHTDCVDTITCAPTEAIRRGIRYWNG
VVPERCRRQFQEGEEWNCFFGYKVYPTLRCPVFVVQWLFDEAQLTVDNVH
LTGQPVQEGLRLYIQNLGRELRHTLKDVPASFAPACLSHEIIIRSHWTDV
QVKGTSLPRALHCWDRSLHDSHKASKTPLKGCPVHLVDSCPWPHCNPSCP
TVRDQFTGQEMNVAQFLMHMGFDMQTVAQPQGLEPSELLGMLSNGS


References
26 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, :, 2022 : PubMed

            

    Title: Structural Analysis and Development of Notum Fragment Screening Hits
    Zhao Y, Mahy W, Willis NJ, Woodward HL, Steadman D, Bayle ED, Atkinson BN, Sipthorp J, Vecchia L and Jones EY <11 more author(s)>
    Ref: ACS Chem Neurosci, 13:2060, 2022 : PubMed

            


Other Papers


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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