UniProtKB - Q6P988 (NOTUM_HUMAN)
Protein
Palmitoleoyl-protein carboxylesterase NOTUM
Gene
NOTUM
Organism
Homo sapiens (Human)
Status
Functioni
Carboxylesterase that acts as a key negative regulator of the Wnt signaling pathway by specifically mediating depalmitoleoylation of WNT proteins. Serine palmitoleoylation of WNT proteins is required for efficient binding to frizzled receptors (PubMed:25731175).1 Publication
Caution
The molecular function of NOTUM has remained unclear for many years. It was initially thought to hydrolyze glycosaminoglycan (GAG) chains of glypicans, thereby affecting glypicans ability to interact with Wnt ligands. It was later reported to trigger glypican shedding, by mediating cleavage of their GPI-anchor. However, while NOTUM specifically inhibit the Wnt signaling pathway, more pleiotropic effects would be expected from an enzyme affecting glypicans. It was finally shown that it requires glypicans to suppress Wnt signaling, but does not cleave their GPI-anchor. It acts by mediating depalmitoleoylation of WNT proteins, impairing WNT binding to frizzled receptors (PubMed:25731175).1 Publication
Catalytic activityi
- [Wnt protein]-O-(9Z)-hexadecenoyl-L-serine + H2O = (9Z)-hexadecenoate + [Wnt protein]-L-serine + H+1 PublicationEC:3.1.1.981 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 232 | Charge relay system1 Publication | 1 | |
Active sitei | 340 | Charge relay system1 Publication | 1 | |
Active sitei | 389 | Charge relay system1 Publication | 1 |
GO - Molecular functioni
- carboxylic ester hydrolase activity Source: GO_Central
- palmitoleyl hydrolase activity Source: UniProtKB
- phospholipase C activity Source: Reactome
GO - Biological processi
- cellular protein metabolic process Source: Reactome
- negative regulation of canonical Wnt signaling pathway Source: GO_Central
- negative regulation of Wnt signaling pathway Source: UniProtKB
- post-translational protein modification Source: Reactome
- protein depalmitoleylation Source: UniProtKB
- Wnt signaling pathway Source: UniProtKB-KW
Keywordsi
Molecular function | Hydrolase, Serine esterase |
Biological process | Wnt signaling pathway |
Enzyme and pathway databases
PathwayCommonsi | Q6P988 |
Reactomei | R-HSA-381426, Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) R-HSA-5362798, Release of Hh-Np from the secreting cell R-HSA-8957275, Post-translational protein phosphorylation |
Protein family/group databases
ESTHERi | human-NOTUM, Pectinacetylesterase-Notum |
Names & Taxonomyi
Protein namesi | Recommended name: Palmitoleoyl-protein carboxylesterase NOTUMCurated (EC:3.1.1.981 Publication)Alternative name(s): hNOTUM1 Publication |
Gene namesi | Name:NOTUMImported ORF Names:OK/SW-CL.301 Publication |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:27106, NOTUM |
MIMi | 609847, gene |
neXtProti | NX_Q6P988 |
VEuPathDBi | HostDB:ENSG00000185269.11 |
Subcellular locationi
Extracellular region or secreted
- Secreted By similarity
Endoplasmic reticulum
- endoplasmic reticulum lumen Source: Reactome
Extracellular region or secreted
- extracellular region Source: Reactome
Keywords - Cellular componenti
SecretedPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 232 | S → A: Abolishes enzyme activity. Unable to mediate serine depalmitoleoylation of WNT proteins. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 147111 |
OpenTargetsi | ENSG00000185269 |
PharmGKBi | PA142671250 |
Miscellaneous databases
Pharosi | Q6P988, Tchem |
Chemistry databases
ChEMBLi | CHEMBL3714531 |
Genetic variation databases
BioMutai | NOTUM |
DMDMi | 182628300 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 19 | Sequence analysisAdd BLAST | 19 | |
ChainiPRO_0000318755 | 20 – 496 | Palmitoleoyl-protein carboxylesterase NOTUMAdd BLAST | 477 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 81 | Phosphoserine; by FAM20C1 Publication | 1 | |
Glycosylationi | 96 | N-linked (GlcNAc...) asparagineCombined sources | 1 |
Keywords - PTMi
Glycoprotein, PhosphoproteinProteomic databases
MassIVEi | Q6P988 |
MaxQBi | Q6P988 |
PaxDbi | Q6P988 |
PeptideAtlasi | Q6P988 |
PRIDEi | Q6P988 |
ProteomicsDBi | 67025 |
PTM databases
GlyGeni | Q6P988, 1 site |
iPTMneti | Q6P988 |
PhosphoSitePlusi | Q6P988 |
Expressioni
Tissue specificityi
Rarely expressed in adult normal tissues.1 Publication
Inductioni
Up-regulated in hepatocellular carcinoma (HCC) with high intracellular beta-catenin.1 Publication
Gene expression databases
Bgeei | ENSG00000185269, Expressed in placenta and 145 other tissues |
ExpressionAtlasi | Q6P988, baseline and differential |
Genevisiblei | Q6P988, HS |
Organism-specific databases
HPAi | ENSG00000185269, Tissue enriched (placenta) |
Interactioni
Binary interactionsi
Q6P988
With | #Exp. | IntAct |
---|---|---|
ZNF655 [Q8N720] | 3 | EBI-16147014,EBI-625509 |
Protein-protein interaction databases
BioGRIDi | 127036, 1 interactor |
DIPi | DIP-61508N |
IntActi | Q6P988, 5 interactors |
STRINGi | 9606.ENSP00000387310 |
Chemistry databases
BindingDBi | Q6P988 |
Miscellaneous databases
RNActi | Q6P988, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q6P988 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Sequence similaritiesi
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | KOG4287, Eukaryota |
GeneTreei | ENSGT00390000015892 |
HOGENOMi | CLU_026533_1_1_1 |
InParanoidi | Q6P988 |
OMAi | VPERCRQ |
OrthoDBi | 610784at2759 |
PhylomeDBi | Q6P988 |
TreeFami | TF324830 |
Family and domain databases
InterProi | View protein in InterPro IPR004963, PAE/NOTUM |
PANTHERi | PTHR21562, PTHR21562, 1 hit |
Pfami | View protein in Pfam PF03283, PAE, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All
Q6P988-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MGRGVRVLLL LSLLHCAGGS EGRKTWRRRG QQPPPPPRTE AAPAAGQPVE
60 70 80 90 100
SFPLDFTAVE GNMDSFMAQV KSLAQSLYPC SAQQLNEDLR LHLLLNTSVT
110 120 130 140 150
CNDGSPAGYY LKESRGSRRW LLFLEGGWYC FNRENCDSRY DTMRRLMSSR
160 170 180 190 200
DWPRTRTGTG ILSSQPEENP YWWNANMVFI PYCSSDVWSG ASSKSEKNEY
210 220 230 240 250
AFMGALIIQE VVRELLGRGL SGAKVLLLAG SSAGGTGVLL NVDRVAEQLE
260 270 280 290 300
KLGYPAIQVR GLADSGWFLD NKQYRHTDCV DTITCAPTEA IRRGIRYWNG
310 320 330 340 350
VVPERCRRQF QEGEEWNCFF GYKVYPTLRC PVFVVQWLFD EAQLTVDNVH
360 370 380 390 400
LTGQPVQEGL RLYIQNLGRE LRHTLKDVPA SFAPACLSHE IIIRSHWTDV
410 420 430 440 450
QVKGTSLPRA LHCWDRSLHD SHKASKTPLK GCPVHLVDSC PWPHCNPSCP
460 470 480 490
TVRDQFTGQE MNVAQFLMHM GFDMQTVAQP QGLEPSELLG MLSNGS
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketC9JYG8 | C9JYG8_HUMAN | Palmitoleoyl-protein carboxylestera... | NOTUM | 295 | Annotation score: | ||
K7EIG3 | K7EIG3_HUMAN | Palmitoleoyl-protein carboxylestera... | NOTUM | 197 | Annotation score: |
Sequence cautioni
The sequence AAH36872 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.Curated
The sequence AAH60882 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.Curated
The sequence BAB93501 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 207 | I → N in AAH36872 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 244 | R → L in AAH36872 (PubMed:15489334).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AC145207 Genomic DNA No translation available. BC036872 mRNA Translation: AAH36872.2 Different initiation. BC060882 mRNA Translation: AAH60882.1 Different initiation. AB062438 mRNA Translation: BAB93501.1 Different initiation. |
CCDSi | CCDS32771.2 |
RefSeqi | NP_848588.3, NM_178493.5 |
Genome annotation databases
Ensembli | ENST00000409678; ENSP00000387310; ENSG00000185269 |
GeneIDi | 147111 |
KEGGi | hsa:147111 |
UCSCi | uc010wvg.3, human |
Similar proteinsi
Cross-referencesi
Web resourcesi
Protein Spotlight The art of biocuration - Issue 177 of March 2016 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AC145207 Genomic DNA No translation available. BC036872 mRNA Translation: AAH36872.2 Different initiation. BC060882 mRNA Translation: AAH60882.1 Different initiation. AB062438 mRNA Translation: BAB93501.1 Different initiation. |
CCDSi | CCDS32771.2 |
RefSeqi | NP_848588.3, NM_178493.5 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
4UYU | X-ray | 2.30 | A/B | 81-451 | [»] | |
4UYW | X-ray | 1.70 | A/B | 81-451 | [»] | |
4UYZ | X-ray | 2.80 | A/B/C/D | 38-496 | [»] | |
4UZ1 | X-ray | 1.40 | A | 81-451 | [»] | |
4UZ5 | X-ray | 2.10 | A | 81-451 | [»] | |
4UZ6 | X-ray | 1.90 | A/B | 81-451 | [»] | |
4UZ7 | X-ray | 2.20 | A/B | 81-451 | [»] | |
4UZ9 | X-ray | 2.20 | A | 81-451 | [»] | |
4UZA | X-ray | 2.40 | A | 81-451 | [»] | |
4UZL | X-ray | 2.10 | A/B | 81-451 | [»] | |
4UZQ | X-ray | 1.50 | A | 81-451 | [»] | |
4WBH | X-ray | 2.20 | A/B | 38-496 | [»] | |
6R8P | X-ray | 1.45 | A | 81-451 | [»] | |
6R8Q | X-ray | 1.50 | A | 81-451 | [»] | |
6R8R | X-ray | 1.27 | A | 81-451 | [»] | |
6T2H | X-ray | 1.41 | A | 81-451 | [»] | |
6T2K | X-ray | 1.38 | A | 81-451 | [»] | |
6TR5 | X-ray | 1.51 | A | 81-451 | [»] | |
6TR6 | X-ray | 1.35 | A | 81-451 | [»] | |
6TR7 | X-ray | 1.47 | A | 81-451 | [»] | |
6TUZ | X-ray | 1.24 | A | 81-451 | [»] | |
6TV4 | X-ray | 1.53 | A | 81-451 | [»] | |
6YSK | X-ray | 1.21 | A | 81-451 | [»] | |
6YUW | X-ray | 1.94 | A | 81-451 | [»] | |
6YUY | X-ray | 2.00 | A | 81-451 | [»] | |
6YV0 | X-ray | 2.00 | A | 81-451 | [»] | |
6YV2 | X-ray | 2.10 | A | 81-451 | [»] | |
6YV4 | X-ray | 2.00 | A | 81-451 | [»] | |
6YXI | X-ray | 1.34 | A | 81-451 | [»] | |
SMRi | Q6P988 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 127036, 1 interactor |
DIPi | DIP-61508N |
IntActi | Q6P988, 5 interactors |
STRINGi | 9606.ENSP00000387310 |
Chemistry databases
BindingDBi | Q6P988 |
ChEMBLi | CHEMBL3714531 |
Protein family/group databases
ESTHERi | human-NOTUM, Pectinacetylesterase-Notum |
PTM databases
GlyGeni | Q6P988, 1 site |
iPTMneti | Q6P988 |
PhosphoSitePlusi | Q6P988 |
Genetic variation databases
BioMutai | NOTUM |
DMDMi | 182628300 |
Proteomic databases
MassIVEi | Q6P988 |
MaxQBi | Q6P988 |
PaxDbi | Q6P988 |
PeptideAtlasi | Q6P988 |
PRIDEi | Q6P988 |
ProteomicsDBi | 67025 |
Protocols and materials databases
Antibodypediai | 19856, 163 antibodies |
DNASUi | 147111 |
Genome annotation databases
Ensembli | ENST00000409678; ENSP00000387310; ENSG00000185269 |
GeneIDi | 147111 |
KEGGi | hsa:147111 |
UCSCi | uc010wvg.3, human |
Organism-specific databases
CTDi | 147111 |
DisGeNETi | 147111 |
GeneCardsi | NOTUM |
HGNCi | HGNC:27106, NOTUM |
HPAi | ENSG00000185269, Tissue enriched (placenta) |
MIMi | 609847, gene |
neXtProti | NX_Q6P988 |
OpenTargetsi | ENSG00000185269 |
PharmGKBi | PA142671250 |
VEuPathDBi | HostDB:ENSG00000185269.11 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG4287, Eukaryota |
GeneTreei | ENSGT00390000015892 |
HOGENOMi | CLU_026533_1_1_1 |
InParanoidi | Q6P988 |
OMAi | VPERCRQ |
OrthoDBi | 610784at2759 |
PhylomeDBi | Q6P988 |
TreeFami | TF324830 |
Enzyme and pathway databases
PathwayCommonsi | Q6P988 |
Reactomei | R-HSA-381426, Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) R-HSA-5362798, Release of Hh-Np from the secreting cell R-HSA-8957275, Post-translational protein phosphorylation |
Miscellaneous databases
BioGRID-ORCSi | 147111, 9 hits in 872 CRISPR screens |
GenomeRNAii | 147111 |
Pharosi | Q6P988, Tchem |
PROi | PR:Q6P988 |
RNActi | Q6P988, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000185269, Expressed in placenta and 145 other tissues |
ExpressionAtlasi | Q6P988, baseline and differential |
Genevisiblei | Q6P988, HS |
Family and domain databases
InterProi | View protein in InterPro IPR004963, PAE/NOTUM |
PANTHERi | PTHR21562, PTHR21562, 1 hit |
Pfami | View protein in Pfam PF03283, PAE, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | NOTUM_HUMAN | |
Accessioni | Q6P988Primary (citable) accession number: Q6P988 Secondary accession number(s): Q8N410, Q8NI82 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 26, 2008 |
Last sequence update: | February 26, 2008 | |
Last modified: | February 10, 2021 | |
This is version 123 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 17
Human chromosome 17: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Protein Spotlight
Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries