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UniProtKB - Q6P988 (NOTUM_HUMAN)

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Protein

Palmitoleoyl-protein carboxylesterase NOTUM

Gene

NOTUM

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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]-O-(9Z)-hexadec-9-enoyl-L-serine + H2O = [Wnt]-L-serine + (9Z)-hexadec-9-enoate.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei232Charge relay system1 Publication1
Active sitei340Charge relay system1 Publication1
Active sitei389Charge relay system1 Publication1

GO - Molecular functioni

  • palmitoleyl hydrolase activity Source: UniProtKB
  • phospholipase C activity Source: Reactome
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionHydrolase, Serine esterase
Biological processWnt signaling pathway

Enzyme and pathway databases

ReactomeiR-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

ESTHERihuman-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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000185269.11
HGNCiHGNC:27106 NOTUM
MIMi609847 gene
neXtProtiNX_Q6P988

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi232S → A: Abolishes enzyme activity. Unable to mediate serine depalmitoleoylation of WNT proteins. 1 Publication1

Organism-specific databases

DisGeNETi147111
OpenTargetsiENSG00000185269
PharmGKBiPA142671250

Chemistry databases

ChEMBLiCHEMBL3714531

Polymorphism and mutation databases

BioMutaiNOTUM
DMDMi182628300

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 19Sequence analysisAdd BLAST19
ChainiPRO_000031875520 – 496Palmitoleoyl-protein carboxylesterase NOTUMAdd BLAST477

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei81Phosphoserine; by FAM20C1 Publication1
Glycosylationi96N-linked (GlcNAc...) asparagineCombined sources1

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ6P988
PaxDbiQ6P988
PeptideAtlasiQ6P988
PRIDEiQ6P988
ProteomicsDBi67025

PTM databases

iPTMnetiQ6P988
PhosphoSitePlusiQ6P988

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

BgeeiENSG00000185269
CleanExiHS_NOTUM
ExpressionAtlasiQ6P988 baseline and differential
GenevisibleiQ6P988 HS

Interactioni

Protein-protein interaction databases

DIPiDIP-61508N
IntActiQ6P988, 5 interactors
STRINGi9606.ENSP00000387310

Chemistry databases

BindingDBiQ6P988

Structurei

Secondary structure

1496
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi85 – 87Combined sources3
Beta strandi89 – 93Combined sources5
Beta strandi95 – 98Combined sources4
Beta strandi104 – 106Combined sources3
Beta strandi108 – 112Combined sources5
Beta strandi119 – 124Combined sources6
Helixi133 – 142Combined sources10
Helixi144 – 146Combined sources3
Beta strandi154 – 156Combined sources3
Helixi160 – 162Combined sources3
Turni166 – 168Combined sources3
Turni170 – 174Combined sources5
Beta strandi175 – 180Combined sources6
Beta strandi184 – 186Combined sources3
Beta strandi196 – 200Combined sources5
Helixi204 – 215Combined sources12
Helixi216 – 218Combined sources3
Helixi220 – 222Combined sources3
Beta strandi224 – 231Combined sources8
Helixi233 – 251Combined sources19
Beta strandi258 – 265Combined sources8
Helixi282 – 285Combined sources4
Helixi287 – 298Combined sources12
Helixi304 – 310Combined sources7
Helixi315 – 319Combined sources5
Helixi321 – 324Combined sources4
Helixi325 – 327Combined sources3
Beta strandi332 – 335Combined sources4
Beta strandi338 – 340Combined sources3
Helixi341 – 346Combined sources6
Beta strandi352 – 354Combined sources3
Helixi358 – 375Combined sources18
Beta strandi379 – 383Combined sources5
Beta strandi385 – 388Combined sources4
Turni395 – 398Combined sources4
Helixi407 – 417Combined sources11
Turni428 – 431Combined sources4
Beta strandi435 – 437Combined sources3
Beta strandi441 – 444Combined sources4

3D structure databases

ProteinModelPortaliQ6P988
SMRiQ6P988
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the pectinacetylesterase family. Notum subfamily.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG4287 Eukaryota
ENOG410XQKD LUCA
GeneTreeiENSGT00390000015892
HOGENOMiHOG000113832
HOVERGENiHBG061551
InParanoidiQ6P988
KOiK19882
OMAiCFNKENC
OrthoDBiEOG091G04KM
PhylomeDBiQ6P988
TreeFamiTF324830

Family and domain databases

InterProiView protein in InterPro
IPR004963 PAE/NOTUM
PANTHERiPTHR21562 PTHR21562, 1 hit
PfamiView protein in Pfam
PF03283 PAE, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q6P988-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:496
Mass (Da):55,699
Last modified:February 26, 2008 - v2
Checksum:i00A7B3FB6436F544
GO

Sequence cautioni

The sequence AAH36872 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAH60882 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAB93501 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti207I → N in AAH36872 (PubMed:15489334).Curated1
Sequence conflicti244R → L in AAH36872 (PubMed:15489334).Curated1

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.
CCDSiCCDS32771.2
RefSeqiNP_848588.3, NM_178493.5
UniGeneiHs.106137

Genome annotation databases

EnsembliENST00000409678; ENSP00000387310; ENSG00000185269
GeneIDi147111
KEGGihsa:147111
UCSCiuc010wvg.3 human

Similar proteinsi

Entry informationi

Entry nameiNOTUM_HUMAN
AccessioniPrimary (citable) accession number: Q6P988
Secondary accession number(s): Q8N410, Q8NI82
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 26, 2008
Last sequence update: February 26, 2008
Last modified: July 18, 2018
This is version 106 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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, Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
  5. SIMILARITY comments
    Index of protein domains and families

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