NOTUM_HUMAN
ID NOTUM_HUMAN Reviewed; 496 AA.
AC Q6P988; Q8N410; Q8NI82;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2008, sequence version 2.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Palmitoleoyl-protein carboxylesterase NOTUM {ECO:0000305};
DE EC=3.1.1.98 {ECO:0000269|PubMed:25731175};
DE AltName: Full=hNOTUM {ECO:0000303|PubMed:25731175};
DE Flags: Precursor;
GN Name=NOTUM {ECO:0000312|HGNC:HGNC:27106};
GN ORFNames=OK/SW-CL.30 {ECO:0000303|Ref.3};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pancreas, and Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 102-496.
RC TISSUE=Colon adenocarcinoma;
RA Shichijo S., Itoh K.;
RT "Identification of immuno-peptidmics that recognized by tumor-reactive CTL
RT generated from TIL of colon cancer patients.";
RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP IDENTIFICATION.
RX PubMed=12015973; DOI=10.1016/s1534-5807(02)00180-6;
RA Giraldez A.J., Copley R.R., Cohen S.M.;
RT "HSPG modification by the secreted enzyme Notum shapes the Wingless
RT morphogen gradient.";
RL Dev. Cell 2:667-676(2002).
RN [5]
RP TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=18429952; DOI=10.1111/j.1349-7006.2008.00814.x;
RA Torisu Y., Watanabe A., Nonaka A., Midorikawa Y., Makuuchi M.,
RA Shimamura T., Sugimura H., Niida A., Akiyama T., Iwanari H., Kodama T.,
RA Zeniya M., Aburatani H.;
RT "Human homolog of NOTUM, overexpressed in hepatocellular carcinoma, is
RT regulated transcriptionally by beta-catenin/TCF.";
RL Cancer Sci. 99:1139-1146(2008).
RN [6]
RP PHOSPHORYLATION AT SER-81.
RX PubMed=26091039; DOI=10.1016/j.cell.2015.05.028;
RA Tagliabracci V.S., Wiley S.E., Guo X., Kinch L.N., Durrant E., Wen J.,
RA Xiao J., Cui J., Nguyen K.B., Engel J.L., Coon J.J., Grishin N.,
RA Pinna L.A., Pagliarini D.J., Dixon J.E.;
RT "A single kinase generates the majority of the secreted phosphoproteome.";
RL Cell 161:1619-1632(2015).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 38-496 IN COMPLEX WITH
RP O-PALMITOLEOYL SERINE, CATALYTIC ACTIVITY, FUNCTION, ACTIVE SITE,
RP GLYCOSYLATION AT ASN-96, AND MUTAGENESIS OF SER-232.
RX PubMed=25731175; DOI=10.1038/nature14259;
RA Kakugawa S., Langton P.F., Zebisch M., Howell S.A., Chang T.H., Liu Y.,
RA Feizi T., Bineva G., O'Reilly N., Snijders A.P., Jones E.Y., Vincent J.P.;
RT "Notum deacylates Wnt proteins to suppress signalling activity.";
RL Nature 519:187-192(2015).
CC -!- FUNCTION: Carboxylesterase that acts as a key negative regulator of the
CC Wnt signaling pathway by specifically mediating depalmitoleoylation of
CC WNT proteins. Serine palmitoleoylation of WNT proteins is required for
CC efficient binding to frizzled receptors (PubMed:25731175).
CC {ECO:0000269|PubMed:25731175}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[Wnt protein]-O-(9Z)-hexadecenoyl-L-serine + H2O = (9Z)-
CC hexadecenoate + [Wnt protein]-L-serine + H(+); Xref=Rhea:RHEA:45340,
CC Rhea:RHEA-COMP:11170, Rhea:RHEA-COMP:11171, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:32372,
CC ChEBI:CHEBI:85189; EC=3.1.1.98;
CC Evidence={ECO:0000269|PubMed:25731175};
CC -!- INTERACTION:
CC Q6P988; Q8N720: ZNF655; NbExp=3; IntAct=EBI-16147014, EBI-625509;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q9VUX3}.
CC -!- TISSUE SPECIFICITY: Rarely expressed in adult normal tissues.
CC {ECO:0000269|PubMed:18429952}.
CC -!- INDUCTION: Up-regulated in hepatocellular carcinoma (HCC) with high
CC intracellular beta-catenin. {ECO:0000269|PubMed:18429952}.
CC -!- SIMILARITY: Belongs to the pectinacetylesterase family. Notum
CC subfamily. {ECO:0000305}.
CC -!- CAUTION: The molecular function of NOTUM has remained unclear for many
CC years. It was initially thought to hydrolyze glycosaminoglycan (GAG)
CC chains of glypicans, thereby affecting glypicans ability to interact
CC with Wnt ligands. It was later reported to trigger glypican shedding,
CC by mediating cleavage of their GPI-anchor. However, while NOTUM
CC specifically inhibit the Wnt signaling pathway, more pleiotropic
CC effects would be expected from an enzyme affecting glypicans. It was
CC finally shown that it requires glypicans to suppress Wnt signaling, but
CC does not cleave their GPI-anchor. It acts by mediating
CC depalmitoleoylation of WNT proteins, impairing WNT binding to frizzled
CC receptors (PubMed:25731175). {ECO:0000269|PubMed:25731175}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH36872.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH60882.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB93501.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=The art of biocuration
CC - Issue 177 of March 2016;
CC URL="https://web.expasy.org/spotlight/back_issues/177/";
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DR EMBL; AC145207; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC036872; AAH36872.2; ALT_INIT; mRNA.
DR EMBL; BC060882; AAH60882.1; ALT_INIT; mRNA.
DR EMBL; AB062438; BAB93501.1; ALT_INIT; mRNA.
DR CCDS; CCDS32771.2; -.
DR RefSeq; NP_848588.3; NM_178493.5.
DR PDB; 4UYU; X-ray; 2.30 A; A/B=81-451.
DR PDB; 4UYW; X-ray; 1.70 A; A/B=81-451.
DR PDB; 4UYZ; X-ray; 2.80 A; A/B/C/D=38-496.
DR PDB; 4UZ1; X-ray; 1.40 A; A=81-451.
DR PDB; 4UZ5; X-ray; 2.10 A; A=81-451.
DR PDB; 4UZ6; X-ray; 1.90 A; A/B=81-451.
DR PDB; 4UZ7; X-ray; 2.20 A; A/B=81-451.
DR PDB; 4UZ9; X-ray; 2.20 A; A=81-451.
DR PDB; 4UZA; X-ray; 2.40 A; A=81-451.
DR PDB; 4UZL; X-ray; 2.10 A; A/B=81-451.
DR PDB; 4UZQ; X-ray; 1.50 A; A=81-451.
DR PDB; 4WBH; X-ray; 2.20 A; A/B=38-496.
DR PDB; 6R8P; X-ray; 1.45 A; A=81-451.
DR PDB; 6R8Q; X-ray; 1.50 A; A=81-451.
DR PDB; 6R8R; X-ray; 1.27 A; A=81-451.
DR PDB; 6T2H; X-ray; 1.41 A; A=81-451.
DR PDB; 6T2K; X-ray; 1.38 A; A=81-451.
DR PDB; 6TR5; X-ray; 1.51 A; A=81-451.
DR PDB; 6TR6; X-ray; 1.35 A; A=81-451.
DR PDB; 6TR7; X-ray; 1.47 A; A=81-451.
DR PDB; 6TUZ; X-ray; 1.24 A; A=81-451.
DR PDB; 6TV4; X-ray; 1.53 A; A=81-451.
DR PDB; 6YSK; X-ray; 1.21 A; A=81-451.
DR PDB; 6YUW; X-ray; 1.94 A; A=81-451.
DR PDB; 6YUY; X-ray; 2.00 A; A=81-451.
DR PDB; 6YV0; X-ray; 2.00 A; A=81-451.
DR PDB; 6YV2; X-ray; 2.10 A; A=81-451.
DR PDB; 6YV4; X-ray; 2.00 A; A=81-451.
DR PDB; 6YXI; X-ray; 1.34 A; A=81-451.
DR PDB; 6ZUV; X-ray; 1.54 A; A=81-451.
DR PDB; 6ZVL; X-ray; 1.30 A; A=81-451.
DR PDB; 6ZYF; X-ray; 2.19 A; A/B=81-451.
DR PDB; 7ARG; X-ray; 1.24 A; A=81-451.
DR PDB; 7B2V; X-ray; 1.24 A; A=81-451.
DR PDB; 7B2Y; X-ray; 1.23 A; A=81-451.
DR PDB; 7B2Z; X-ray; 1.24 A; A=81-451.
DR PDB; 7B37; X-ray; 1.34 A; A=81-451.
DR PDB; 7B3F; X-ray; 1.39 A; A=81-451.
DR PDB; 7B3G; X-ray; 1.28 A; A=81-451.
DR PDB; 7B3H; X-ray; 1.28 A; A=81-451.
DR PDB; 7B3I; X-ray; 1.34 A; A=81-451.
DR PDB; 7B3P; X-ray; 1.28 A; A=81-451.
DR PDB; 7B3X; X-ray; 1.34 A; A=81-451.
DR PDB; 7B45; X-ray; 1.38 A; A=81-451.
DR PDB; 7B4X; X-ray; 1.24 A; A=81-451.
DR PDB; 7B50; X-ray; 1.33 A; A=81-451.
DR PDB; 7B7W; X-ray; 1.60 A; A=81-451.
DR PDB; 7B7X; X-ray; 2.41 A; A=81-451.
DR PDB; 7B7Y; X-ray; 1.48 A; A=81-451.
DR PDB; 7B84; X-ray; 1.36 A; A=81-451.
DR PDB; 7B86; X-ray; 1.40 A; A=81-451.
DR PDB; 7B87; X-ray; 1.58 A; A=81-451.
DR PDB; 7B89; X-ray; 1.84 A; A=81-451.
DR PDB; 7B8A; X-ray; 1.23 A; A=81-451.
DR PDB; 7B8C; X-ray; 1.43 A; A=81-451.
DR PDB; 7B8D; X-ray; 1.62 A; A=81-451.
DR PDB; 7B8F; X-ray; 1.62 A; A=81-451.
DR PDB; 7B8G; X-ray; 1.58 A; A=81-451.
DR PDB; 7B8J; X-ray; 1.75 A; A=81-451.
DR PDB; 7B8K; X-ray; 1.60 A; A=81-451.
DR PDB; 7B8L; X-ray; 1.45 A; A=81-451.
DR PDB; 7B8M; X-ray; 1.48 A; A=81-451.
DR PDB; 7B8N; X-ray; 1.56 A; A=81-451.
DR PDB; 7B8O; X-ray; 1.50 A; A=81-451.
DR PDB; 7B8U; X-ray; 1.54 A; A=81-451.
DR PDB; 7B8X; X-ray; 1.51 A; A=81-451.
DR PDB; 7B8Y; X-ray; 1.57 A; A=81-451.
DR PDB; 7B8Z; X-ray; 1.73 A; A=81-451.
DR PDB; 7B98; X-ray; 1.53 A; A=81-451.
DR PDB; 7B99; X-ray; 1.81 A; A=81-451.
DR PDB; 7B9D; X-ray; 1.93 A; A=81-451.
DR PDB; 7B9I; X-ray; 1.34 A; A=81-451.
DR PDB; 7B9N; X-ray; 1.38 A; A=81-451.
DR PDB; 7B9U; X-ray; 1.50 A; A=81-451.
DR PDB; 7BA1; X-ray; 1.93 A; A=81-451.
DR PDB; 7BAC; X-ray; 1.54 A; A=81-451.
DR PDB; 7BAP; X-ray; 1.53 A; A=81-451.
DR PDB; 7BC8; X-ray; 1.74 A; A=81-451.
DR PDB; 7BC9; X-ray; 1.73 A; A=81-451.
DR PDB; 7BCC; X-ray; 1.58 A; A=81-451.
DR PDB; 7BCD; X-ray; 1.51 A; A=81-451.
DR PDB; 7BCF; X-ray; 1.86 A; A=81-451.
DR PDB; 7BCH; X-ray; 1.70 A; A=81-451.
DR PDB; 7BCI; X-ray; 1.94 A; A=81-451.
DR PDB; 7BCK; X-ray; 1.70 A; A=81-451.
DR PDB; 7BCL; X-ray; 1.84 A; A=81-451.
DR PDB; 7BD2; X-ray; 1.52 A; A=81-451.
DR PDB; 7BD3; X-ray; 1.91 A; A=81-451.
DR PDB; 7BD4; X-ray; 1.80 A; A=81-451.
DR PDB; 7BD5; X-ray; 1.69 A; A=81-451.
DR PDB; 7BD6; X-ray; 1.70 A; A=81-451.
DR PDB; 7BD8; X-ray; 1.42 A; A=81-451.
DR PDB; 7BD9; X-ray; 1.59 A; A=81-451.
DR PDB; 7BDA; X-ray; 1.47 A; A=81-451.
DR PDB; 7BDB; X-ray; 1.46 A; A=81-451.
DR PDB; 7BDC; X-ray; 1.32 A; A=81-451.
DR PDB; 7BDD; X-ray; 1.47 A; A=81-451.
DR PDB; 7BDF; X-ray; 1.40 A; A=81-451.
DR PDB; 7BDG; X-ray; 1.60 A; A=81-451.
DR PDB; 7BDH; X-ray; 1.54 A; A=81-451.
DR PDB; 7BLI; X-ray; 1.47 A; A=81-451.
DR PDB; 7BLS; X-ray; 1.19 A; A=81-451.
DR PDB; 7BLT; X-ray; 1.20 A; A=81-451.
DR PDB; 7BLU; X-ray; 1.21 A; A=81-451.
DR PDB; 7BLW; X-ray; 1.45 A; A=81-451.
DR PDB; 7BM1; X-ray; 1.37 A; A=81-451.
DR PDB; 7BM3; X-ray; 1.40 A; A=81-451.
DR PDB; 7BM7; X-ray; 1.87 A; A=81-451.
DR PDB; 7BMB; X-ray; 1.83 A; A=81-451.
DR PDB; 7BMD; X-ray; 1.45 A; A=81-451.
DR PDB; 7BN5; X-ray; 2.22 A; A=81-451.
DR PDB; 7BN8; X-ray; 1.78 A; A=81-451.
DR PDB; 7BNB; X-ray; 1.16 A; A=81-451.
DR PDB; 7BNC; X-ray; 1.86 A; A=81-451.
DR PDB; 7BND; X-ray; 2.10 A; A=81-451.
DR PDB; 7BNE; X-ray; 1.70 A; A=81-451.
DR PDB; 7BNF; X-ray; 1.45 A; A=81-451.
DR PDB; 7BNJ; X-ray; 1.49 A; A=81-451.
DR PDB; 7BNL; X-ray; 1.23 A; A=81-451.
DR PDB; 7BO1; X-ray; 1.40 A; A=81-451.
DR PDB; 7BO2; X-ray; 1.21 A; A=81-451.
DR PDB; 7BO5; X-ray; 1.38 A; A=81-451.
DR PDBsum; 4UYU; -.
DR PDBsum; 4UYW; -.
DR PDBsum; 4UYZ; -.
DR PDBsum; 4UZ1; -.
DR PDBsum; 4UZ5; -.
DR PDBsum; 4UZ6; -.
DR PDBsum; 4UZ7; -.
DR PDBsum; 4UZ9; -.
DR PDBsum; 4UZA; -.
DR PDBsum; 4UZL; -.
DR PDBsum; 4UZQ; -.
DR PDBsum; 4WBH; -.
DR PDBsum; 6R8P; -.
DR PDBsum; 6R8Q; -.
DR PDBsum; 6R8R; -.
DR PDBsum; 6T2H; -.
DR PDBsum; 6T2K; -.
DR PDBsum; 6TR5; -.
DR PDBsum; 6TR6; -.
DR PDBsum; 6TR7; -.
DR PDBsum; 6TUZ; -.
DR PDBsum; 6TV4; -.
DR PDBsum; 6YSK; -.
DR PDBsum; 6YUW; -.
DR PDBsum; 6YUY; -.
DR PDBsum; 6YV0; -.
DR PDBsum; 6YV2; -.
DR PDBsum; 6YV4; -.
DR PDBsum; 6YXI; -.
DR PDBsum; 6ZUV; -.
DR PDBsum; 6ZVL; -.
DR PDBsum; 6ZYF; -.
DR PDBsum; 7ARG; -.
DR PDBsum; 7B2V; -.
DR PDBsum; 7B2Y; -.
DR PDBsum; 7B2Z; -.
DR PDBsum; 7B37; -.
DR PDBsum; 7B3F; -.
DR PDBsum; 7B3G; -.
DR PDBsum; 7B3H; -.
DR PDBsum; 7B3I; -.
DR PDBsum; 7B3P; -.
DR PDBsum; 7B3X; -.
DR PDBsum; 7B45; -.
DR PDBsum; 7B4X; -.
DR PDBsum; 7B50; -.
DR PDBsum; 7B7W; -.
DR PDBsum; 7B7X; -.
DR PDBsum; 7B7Y; -.
DR PDBsum; 7B84; -.
DR PDBsum; 7B86; -.
DR PDBsum; 7B87; -.
DR PDBsum; 7B89; -.
DR PDBsum; 7B8A; -.
DR PDBsum; 7B8C; -.
DR PDBsum; 7B8D; -.
DR PDBsum; 7B8F; -.
DR PDBsum; 7B8G; -.
DR PDBsum; 7B8J; -.
DR PDBsum; 7B8K; -.
DR PDBsum; 7B8L; -.
DR PDBsum; 7B8M; -.
DR PDBsum; 7B8N; -.
DR PDBsum; 7B8O; -.
DR PDBsum; 7B8U; -.
DR PDBsum; 7B8X; -.
DR PDBsum; 7B8Y; -.
DR PDBsum; 7B8Z; -.
DR PDBsum; 7B98; -.
DR PDBsum; 7B99; -.
DR PDBsum; 7B9D; -.
DR PDBsum; 7B9I; -.
DR PDBsum; 7B9N; -.
DR PDBsum; 7B9U; -.
DR PDBsum; 7BA1; -.
DR PDBsum; 7BAC; -.
DR PDBsum; 7BAP; -.
DR PDBsum; 7BC8; -.
DR PDBsum; 7BC9; -.
DR PDBsum; 7BCC; -.
DR PDBsum; 7BCD; -.
DR PDBsum; 7BCF; -.
DR PDBsum; 7BCH; -.
DR PDBsum; 7BCI; -.
DR PDBsum; 7BCK; -.
DR PDBsum; 7BCL; -.
DR PDBsum; 7BD2; -.
DR PDBsum; 7BD3; -.
DR PDBsum; 7BD4; -.
DR PDBsum; 7BD5; -.
DR PDBsum; 7BD6; -.
DR PDBsum; 7BD8; -.
DR PDBsum; 7BD9; -.
DR PDBsum; 7BDA; -.
DR PDBsum; 7BDB; -.
DR PDBsum; 7BDC; -.
DR PDBsum; 7BDD; -.
DR PDBsum; 7BDF; -.
DR PDBsum; 7BDG; -.
DR PDBsum; 7BDH; -.
DR PDBsum; 7BLI; -.
DR PDBsum; 7BLS; -.
DR PDBsum; 7BLT; -.
DR PDBsum; 7BLU; -.
DR PDBsum; 7BLW; -.
DR PDBsum; 7BM1; -.
DR PDBsum; 7BM3; -.
DR PDBsum; 7BM7; -.
DR PDBsum; 7BMB; -.
DR PDBsum; 7BMD; -.
DR PDBsum; 7BN5; -.
DR PDBsum; 7BN8; -.
DR PDBsum; 7BNB; -.
DR PDBsum; 7BNC; -.
DR PDBsum; 7BND; -.
DR PDBsum; 7BNE; -.
DR PDBsum; 7BNF; -.
DR PDBsum; 7BNJ; -.
DR PDBsum; 7BNL; -.
DR PDBsum; 7BO1; -.
DR PDBsum; 7BO2; -.
DR PDBsum; 7BO5; -.
DR AlphaFoldDB; Q6P988; -.
DR SMR; Q6P988; -.
DR BioGRID; 127036; 4.
DR DIP; DIP-61508N; -.
DR IntAct; Q6P988; 5.
DR STRING; 9606.ENSP00000387310; -.
DR BindingDB; Q6P988; -.
DR ChEMBL; CHEMBL3714531; -.
DR ESTHER; human-NOTUM; Pectinacetylesterase-Notum.
DR GlyGen; Q6P988; 1 site.
DR iPTMnet; Q6P988; -.
DR PhosphoSitePlus; Q6P988; -.
DR BioMuta; NOTUM; -.
DR DMDM; 182628300; -.
DR MassIVE; Q6P988; -.
DR MaxQB; Q6P988; -.
DR PaxDb; Q6P988; -.
DR PeptideAtlas; Q6P988; -.
DR PRIDE; Q6P988; -.
DR ProteomicsDB; 67025; -.
DR Antibodypedia; 19856; 156 antibodies from 28 providers.
DR DNASU; 147111; -.
DR Ensembl; ENST00000409678.8; ENSP00000387310.3; ENSG00000185269.12.
DR GeneID; 147111; -.
DR KEGG; hsa:147111; -.
DR MANE-Select; ENST00000409678.8; ENSP00000387310.3; NM_178493.6; NP_848588.3.
DR UCSC; uc010wvg.3; human.
DR CTD; 147111; -.
DR DisGeNET; 147111; -.
DR GeneCards; NOTUM; -.
DR HGNC; HGNC:27106; NOTUM.
DR HPA; ENSG00000185269; Tissue enriched (placenta).
DR MIM; 609847; gene.
DR neXtProt; NX_Q6P988; -.
DR OpenTargets; ENSG00000185269; -.
DR PharmGKB; PA142671250; -.
DR VEuPathDB; HostDB:ENSG00000185269; -.
DR eggNOG; KOG4287; Eukaryota.
DR GeneTree; ENSGT00390000015892; -.
DR HOGENOM; CLU_026533_1_1_1; -.
DR InParanoid; Q6P988; -.
DR OMA; ENCDTRY; -.
DR OrthoDB; 610784at2759; -.
DR PhylomeDB; Q6P988; -.
DR TreeFam; TF324830; -.
DR BRENDA; 3.1.1.98; 2681.
DR PathwayCommons; Q6P988; -.
DR Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-HSA-5362798; Release of Hh-Np from the secreting cell.
DR Reactome; R-HSA-8957275; Post-translational protein phosphorylation.
DR SignaLink; Q6P988; -.
DR BioGRID-ORCS; 147111; 17 hits in 1073 CRISPR screens.
DR GenomeRNAi; 147111; -.
DR Pharos; Q6P988; Tchem.
DR PRO; PR:Q6P988; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q6P988; protein.
DR Bgee; ENSG00000185269; Expressed in decidua and 116 other tissues.
DR ExpressionAtlas; Q6P988; baseline and differential.
DR Genevisible; Q6P988; HS.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:1990699; F:palmitoleyl hydrolase activity; IDA:UniProtKB.
DR GO; GO:0004629; F:phospholipase C activity; TAS:Reactome.
DR GO; GO:0060348; P:bone development; IMP:MGI.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IBA:GO_Central.
DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:1990697; P:protein depalmitoleylation; IDA:UniProtKB.
DR GO; GO:0030500; P:regulation of bone mineralization; IDA:MGI.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR InterPro; IPR004963; PAE/NOTUM.
DR PANTHER; PTHR21562; PTHR21562; 1.
DR Pfam; PF03283; PAE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Glycoprotein; Hydrolase; Phosphoprotein; Reference proteome;
KW Secreted; Serine esterase; Signal; Wnt signaling pathway.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..496
FT /note="Palmitoleoyl-protein carboxylesterase NOTUM"
FT /id="PRO_0000318755"
FT REGION 21..46
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 232
FT /note="Charge relay system"
FT /evidence="ECO:0000269|PubMed:25731175"
FT ACT_SITE 340
FT /note="Charge relay system"
FT /evidence="ECO:0000269|PubMed:25731175"
FT ACT_SITE 389
FT /note="Charge relay system"
FT /evidence="ECO:0000269|PubMed:25731175"
FT MOD_RES 81
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT CARBOHYD 96
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0007744|PDB:4UYU, ECO:0007744|PDB:4UYW,
FT ECO:0007744|PDB:4UYZ, ECO:0007744|PDB:4UZ1,
FT ECO:0007744|PDB:4UZ5, ECO:0007744|PDB:4UZ6,
FT ECO:0007744|PDB:4UZ9, ECO:0007744|PDB:4UZA,
FT ECO:0007744|PDB:4UZL, ECO:0007744|PDB:4UZQ"
FT MUTAGEN 232
FT /note="S->A: Abolishes enzyme activity. Unable to mediate
FT serine depalmitoleoylation of WNT proteins."
FT /evidence="ECO:0000269|PubMed:25731175"
FT CONFLICT 207
FT /note="I -> N (in Ref. 2; AAH36872)"
FT /evidence="ECO:0000305"
FT CONFLICT 244
FT /note="R -> L (in Ref. 2; AAH36872)"
FT /evidence="ECO:0000305"
FT HELIX 85..87
FT /evidence="ECO:0007829|PDB:4UZA"
FT STRAND 89..93
FT /evidence="ECO:0007829|PDB:6YSK"
FT STRAND 95..98
FT /evidence="ECO:0007829|PDB:4WBH"
FT STRAND 104..106
FT /evidence="ECO:0007829|PDB:7B2Y"
FT STRAND 108..112
FT /evidence="ECO:0007829|PDB:6YSK"
FT STRAND 119..124
FT /evidence="ECO:0007829|PDB:6YSK"
FT HELIX 133..142
FT /evidence="ECO:0007829|PDB:6YSK"
FT HELIX 144..146
FT /evidence="ECO:0007829|PDB:6YSK"
FT STRAND 154..156
FT /evidence="ECO:0007829|PDB:6YSK"
FT HELIX 160..162
FT /evidence="ECO:0007829|PDB:6YSK"
FT TURN 166..168
FT /evidence="ECO:0007829|PDB:6YSK"
FT TURN 170..174
FT /evidence="ECO:0007829|PDB:6YSK"
FT STRAND 175..180
FT /evidence="ECO:0007829|PDB:6YSK"
FT STRAND 184..186
FT /evidence="ECO:0007829|PDB:6YSK"
FT STRAND 198..200
FT /evidence="ECO:0007829|PDB:7B2Y"
FT HELIX 204..216
FT /evidence="ECO:0007829|PDB:6YSK"
FT TURN 217..219
FT /evidence="ECO:0007829|PDB:6YSK"
FT HELIX 220..222
FT /evidence="ECO:0007829|PDB:6YSK"
FT STRAND 224..231
FT /evidence="ECO:0007829|PDB:6YSK"
FT HELIX 233..252
FT /evidence="ECO:0007829|PDB:6YSK"
FT STRAND 257..265
FT /evidence="ECO:0007829|PDB:6YSK"
FT STRAND 279..281
FT /evidence="ECO:0007829|PDB:7B2Y"
FT TURN 282..284
FT /evidence="ECO:0007829|PDB:7B2Y"
FT HELIX 287..298
FT /evidence="ECO:0007829|PDB:6YSK"
FT HELIX 304..310
FT /evidence="ECO:0007829|PDB:6YSK"
FT HELIX 315..319
FT /evidence="ECO:0007829|PDB:6YSK"
FT HELIX 321..324
FT /evidence="ECO:0007829|PDB:6YSK"
FT HELIX 325..327
FT /evidence="ECO:0007829|PDB:6YSK"
FT STRAND 332..335
FT /evidence="ECO:0007829|PDB:6YSK"
FT STRAND 338..340
FT /evidence="ECO:0007829|PDB:4UZL"
FT HELIX 341..346
FT /evidence="ECO:0007829|PDB:6YSK"
FT STRAND 352..354
FT /evidence="ECO:0007829|PDB:6YV0"
FT HELIX 358..375
FT /evidence="ECO:0007829|PDB:6YSK"
FT STRAND 379..383
FT /evidence="ECO:0007829|PDB:6YSK"
FT STRAND 385..388
FT /evidence="ECO:0007829|PDB:4UZL"
FT TURN 395..398
FT /evidence="ECO:0007829|PDB:6YSK"
FT HELIX 407..417
FT /evidence="ECO:0007829|PDB:6YSK"
FT TURN 428..431
FT /evidence="ECO:0007829|PDB:4UZ7"
FT STRAND 435..437
FT /evidence="ECO:0007829|PDB:6YSK"
FT STRAND 441..444
FT /evidence="ECO:0007829|PDB:4UZL"
SQ SEQUENCE 496 AA; 55699 MW; 00A7B3FB6436F544 CRC64;
MGRGVRVLLL LSLLHCAGGS EGRKTWRRRG QQPPPPPRTE AAPAAGQPVE SFPLDFTAVE
GNMDSFMAQV KSLAQSLYPC SAQQLNEDLR LHLLLNTSVT CNDGSPAGYY LKESRGSRRW
LLFLEGGWYC FNRENCDSRY DTMRRLMSSR DWPRTRTGTG ILSSQPEENP YWWNANMVFI
PYCSSDVWSG ASSKSEKNEY AFMGALIIQE VVRELLGRGL SGAKVLLLAG SSAGGTGVLL
NVDRVAEQLE KLGYPAIQVR GLADSGWFLD NKQYRHTDCV DTITCAPTEA IRRGIRYWNG
VVPERCRRQF QEGEEWNCFF GYKVYPTLRC PVFVVQWLFD EAQLTVDNVH LTGQPVQEGL
RLYIQNLGRE LRHTLKDVPA SFAPACLSHE IIIRSHWTDV QVKGTSLPRA LHCWDRSLHD
SHKASKTPLK GCPVHLVDSC PWPHCNPSCP TVRDQFTGQE MNVAQFLMHM GFDMQTVAQP
QGLEPSELLG MLSNGS
