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Protein

Palmitoleoyl-protein carboxylesterase NOTUM

Gene

NOTUM

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Carboxylesterase that acts as a key negative regulator of the Wnt signaling pathway by specifically mediating depalmitoleylation of WNT proteins. Serine palmitoleylation of WNT proteins is required for efficient 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)LengthDescriptionGraphical viewFeature identifierActions
Active sitei232 – 2321Charge relay system1 Publication
Active sitei340 – 3401Charge relay system1 Publication
Active sitei389 – 3891Charge relay system1 Publication

GO - Molecular functioni

  • palmitoleyl hydrolase activity Source: UniProtKB
  • phospholipase C activity Source: Reactome

GO - Biological processi

  • negative regulation of Wnt signaling pathway Source: UniProtKB
  • protein depalmitoleylation Source: UniProtKB
  • Wnt signaling pathway Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Serine esterase

Keywords - Biological processi

Wnt signaling pathway

Enzyme and pathway databases

ReactomeiR-HSA-5362798. Release of Hh-Np from the secreting cell.

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:27106. NOTUM.

Subcellular locationi

  • Secreted By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi232 – 2321S → A: Abolishes enzyme activity. Unable to mediate serine depalmitoleylation of WNT proteins. 1 Publication

Organism-specific databases

PharmGKBiPA142671250.

Polymorphism and mutation databases

BioMutaiNOTUM.
DMDMi182628300.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1919Sequence analysisAdd
BLAST
Chaini20 – 496477Palmitoleoyl-protein carboxylesterase NOTUMPRO_0000318755Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei81 – 811Phosphoserine; by FAM20C1 Publication
Glycosylationi96 – 961N-linked (GlcNAc...)Combined sources

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ6P988.
PaxDbiQ6P988.
PRIDEiQ6P988.

PTM databases

iPTMnetiQ6P988.

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

BgeeiQ6P988.
CleanExiHS_NOTUM.
ExpressionAtlasiQ6P988. baseline and differential.
GenevisibleiQ6P988. HS.

Organism-specific databases

HPAiHPA023041.
HPA053024.

Interactioni

Protein-protein interaction databases

DIPiDIP-61508N.
STRINGi9606.ENSP00000387310.

Structurei

Secondary structure

1
496
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi85 – 873Combined sources
Beta strandi89 – 935Combined sources
Beta strandi95 – 984Combined sources
Beta strandi104 – 1063Combined sources
Beta strandi108 – 1125Combined sources
Beta strandi119 – 1246Combined sources
Helixi133 – 14210Combined sources
Helixi144 – 1463Combined sources
Beta strandi154 – 1563Combined sources
Helixi160 – 1623Combined sources
Turni166 – 1683Combined sources
Turni170 – 1745Combined sources
Beta strandi175 – 1806Combined sources
Beta strandi184 – 1863Combined sources
Beta strandi196 – 2005Combined sources
Helixi204 – 21512Combined sources
Helixi216 – 2183Combined sources
Helixi220 – 2223Combined sources
Beta strandi224 – 2318Combined sources
Helixi233 – 25119Combined sources
Beta strandi258 – 2658Combined sources
Helixi282 – 2854Combined sources
Helixi287 – 29812Combined sources
Helixi304 – 3107Combined sources
Helixi315 – 3195Combined sources
Helixi321 – 3244Combined sources
Helixi325 – 3273Combined sources
Beta strandi332 – 3354Combined sources
Beta strandi338 – 3403Combined sources
Helixi341 – 3466Combined sources
Beta strandi352 – 3543Combined sources
Helixi358 – 37518Combined sources
Beta strandi379 – 3835Combined sources
Beta strandi385 – 3884Combined sources
Turni395 – 3984Combined sources
Helixi407 – 41711Combined sources
Turni428 – 4314Combined sources
Beta strandi435 – 4373Combined sources
Beta strandi441 – 4444Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4UYUX-ray2.30A/B81-451[»]
4UYWX-ray1.70A/B81-451[»]
4UYZX-ray2.80A/B/C/D38-496[»]
4UZ1X-ray1.40A81-451[»]
4UZ5X-ray2.10A81-451[»]
4UZ6X-ray1.90A/B81-451[»]
4UZ7X-ray2.20A/B81-451[»]
4UZ9X-ray2.20A81-451[»]
4UZAX-ray2.40A81-451[»]
4UZLX-ray2.10A/B81-451[»]
4UZQX-ray1.50A81-451[»]
4WBHX-ray2.20A/B38-496[»]
ProteinModelPortaliQ6P988.
SMRiQ6P988. Positions 87-451.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG4287. Eukaryota.
ENOG410XQKD. LUCA.
GeneTreeiENSGT00390000015892.
HOGENOMiHOG000113832.
HOVERGENiHBG061551.
InParanoidiQ6P988.
KOiK19882.
OMAiCFNKENC.
OrthoDBiEOG76X60F.
PhylomeDBiQ6P988.
TreeFamiTF324830.

Family and domain databases

InterProiIPR004963. PAE/NOTUM.
[Graphical view]
PANTHERiPTHR21562. PTHR21562. 1 hit.
PfamiPF03283. PAE. 1 hit.
[Graphical view]

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 AAH36872.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAH60882.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAB93501.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti207 – 2071I → N in AAH36872 (PubMed:15489334).Curated
Sequence conflicti244 – 2441R → L in AAH36872 (PubMed:15489334).Curated

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.
XP_011521839.1. XM_011523537.1.
UniGeneiHs.106137.

Genome annotation databases

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

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.
CCDSiCCDS32771.2.
RefSeqiNP_848588.3. NM_178493.5.
XP_011521839.1. XM_011523537.1.
UniGeneiHs.106137.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4UYUX-ray2.30A/B81-451[»]
4UYWX-ray1.70A/B81-451[»]
4UYZX-ray2.80A/B/C/D38-496[»]
4UZ1X-ray1.40A81-451[»]
4UZ5X-ray2.10A81-451[»]
4UZ6X-ray1.90A/B81-451[»]
4UZ7X-ray2.20A/B81-451[»]
4UZ9X-ray2.20A81-451[»]
4UZAX-ray2.40A81-451[»]
4UZLX-ray2.10A/B81-451[»]
4UZQX-ray1.50A81-451[»]
4WBHX-ray2.20A/B38-496[»]
ProteinModelPortaliQ6P988.
SMRiQ6P988. Positions 87-451.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-61508N.
STRINGi9606.ENSP00000387310.

Protein family/group databases

ESTHERihuman-NOTUM. Pectinacetylesterase-Notum.

PTM databases

iPTMnetiQ6P988.

Polymorphism and mutation databases

BioMutaiNOTUM.
DMDMi182628300.

Proteomic databases

MaxQBiQ6P988.
PaxDbiQ6P988.
PRIDEiQ6P988.

Protocols and materials databases

DNASUi147111.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi147111.
GeneCardsiNOTUM.
HGNCiHGNC:27106. NOTUM.
HPAiHPA023041.
HPA053024.
MIMi609847. gene.
neXtProtiNX_Q6P988.
PharmGKBiPA142671250.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4287. Eukaryota.
ENOG410XQKD. LUCA.
GeneTreeiENSGT00390000015892.
HOGENOMiHOG000113832.
HOVERGENiHBG061551.
InParanoidiQ6P988.
KOiK19882.
OMAiCFNKENC.
OrthoDBiEOG76X60F.
PhylomeDBiQ6P988.
TreeFamiTF324830.

Enzyme and pathway databases

ReactomeiR-HSA-5362798. Release of Hh-Np from the secreting cell.

Miscellaneous databases

GenomeRNAii147111.
PROiQ6P988.
SOURCEiSearch...

Gene expression databases

BgeeiQ6P988.
CleanExiHS_NOTUM.
ExpressionAtlasiQ6P988. baseline and differential.
GenevisibleiQ6P988. HS.

Family and domain databases

InterProiIPR004963. PAE/NOTUM.
[Graphical view]
PANTHERiPTHR21562. PTHR21562. 1 hit.
PfamiPF03283. PAE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
    Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L.
    , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
    Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Pancreas and Placenta.
  3. "Identification of immuno-peptidmics that recognized by tumor-reactive CTL generated from TIL of colon cancer patients."
    Shichijo S., Itoh K.
    Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 102-496.
    Tissue: Colon adenocarcinoma.
  4. "HSPG modification by the secreted enzyme Notum shapes the Wingless morphogen gradient."
    Giraldez A.J., Copley R.R., Cohen S.M.
    Dev. Cell 2:667-676(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION.
  5. "Human homolog of NOTUM, overexpressed in hepatocellular carcinoma, is regulated transcriptionally by beta-catenin/TCF."
    Torisu Y., Watanabe A., Nonaka A., Midorikawa Y., Makuuchi M., Shimamura T., Sugimura H., Niida A., Akiyama T., Iwanari H., Kodama T., Zeniya M., Aburatani H.
    Cancer Sci. 99:1139-1146(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY, INDUCTION.
  6. Cited for: PHOSPHORYLATION AT SER-81.
  7. Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 38-496 IN COMPLEX WITH O-PALMITOLEOYL SERINE, CATALYTIC ACTIVITY, FUNCTION, ACTIVE SITE, GLYCOSYLATION AT ASN-96, MUTAGENESIS OF SER-232.

Entry informationi

Entry nameiNOTUM_HUMAN
AccessioniPrimary (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: June 8, 2016
This is version 90 of the entry and version 2 of the sequence. [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

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 depalmitoleylation of WNT proteins, impairing WNT binding to frizzled receptors (PubMed:25731175).1 Publication

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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.