NOT1A_DANRE
ID NOT1A_DANRE Reviewed; 500 AA.
AC C5H5C4;
DT 29-APR-2015, integrated into UniProtKB/Swiss-Prot.
DT 28-JUL-2009, sequence version 1.
DT 03-AUG-2022, entry version 67.
DE RecName: Full=Palmitoleoyl-protein carboxylesterase notum1a {ECO:0000250|UniProtKB:Q6P988};
DE EC=3.1.1.98 {ECO:0000250|UniProtKB:Q6P988};
DE Flags: Precursor;
GN Name=notum1a {ECO:0000312|ZFIN:ZDB-GENE-120807-2};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=22669824; DOI=10.1242/dev.063206;
RA Flowers G.P., Topczewska J.M., Topczewski J.;
RT "A zebrafish Notum homolog specifically blocks the Wnt/?-catenin signaling
RT pathway.";
RL Development 139:2416-2425(2012).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
CC -!- FUNCTION: Carboxylesterase that acts as a key negative regulator of the
CC Wnt signaling pathway (PubMed:22669824). Acts by specifically mediating
CC depalmitoleoylation of WNT proteins. Serine palmitoleoylation of WNT
CC proteins is required for efficient binding to frizzled receptors (By
CC similarity). {ECO:0000250|UniProtKB:Q6P988,
CC ECO:0000269|PubMed:22669824}.
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:0000250|UniProtKB:Q6P988};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q9VUX3}.
CC -!- DEVELOPMENTAL STAGE: First appears around the blastoderm margin prior
CC to the onset of gastrulation. In later gastrulation, expressed in the
CC lateral edges and midline of the posterior neural plate. During
CC segmentation, expressed in stripes at the lateral edges and adjacent to
CC the midline of the neural plate, throughout the hindbrain, with strong
CC expression in rhombomeres 3 and 5, and at the midbrain-hindbrain
CC boundary. At 24 hours post-fertilization (hpf), highly expressed in the
CC central nervous system, including the dorsal neural tube and the
CC midbrain-hindbrain boundary. {ECO:0000269|PubMed:22669824}.
CC -!- SIMILARITY: Belongs to the pectinacetylesterase family. Notum
CC subfamily. {ECO:0000305}.
CC -!- CAUTION: The molecular function of NOTUM family protein has remained
CC unclear for many years. It was initially thought to hydrolyze
CC glycosaminoglycan (GAG) chains of glypicans, thereby affecting
CC glypicans ability to interact with Wnt ligands. It was later reported
CC to trigger glypican shedding, by mediating cleavage of their GPI-anchor
CC (PubMed:22669824). It was finally shown that it requires glypicans to
CC suppress Wnt signaling, but does not cleave their GPI-anchor. It acts
CC by mediating depalmitoleoylation of WNT proteins, impairing WNT binding
CC to frizzled receptors. {ECO:0000269|PubMed:22669824, ECO:0000305}.
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DR EMBL; EU728672; ACH92954.1; -; mRNA.
DR EMBL; AL954343; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_001155126.1; NM_001161654.1.
DR AlphaFoldDB; C5H5C4; -.
DR SMR; C5H5C4; -.
DR STRING; 7955.ENSDARP00000047417; -.
DR ESTHER; danre-c5h5c4; Pectinacetylesterase-Notum.
DR PaxDb; C5H5C4; -.
DR Ensembl; ENSDART00000047418; ENSDARP00000047417; ENSDARG00000031126.
DR GeneID; 570510; -.
DR KEGG; dre:570510; -.
DR CTD; 570510; -.
DR ZFIN; ZDB-GENE-120807-2; notum1a.
DR eggNOG; KOG4287; Eukaryota.
DR GeneTree; ENSGT00390000015892; -.
DR HOGENOM; CLU_026533_1_1_1; -.
DR InParanoid; C5H5C4; -.
DR OMA; ENCDTRY; -.
DR OrthoDB; 610784at2759; -.
DR PhylomeDB; C5H5C4; -.
DR TreeFam; TF324830; -.
DR BRENDA; 3.1.1.98; 928.
DR Reactome; R-DRE-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-DRE-5362798; Release of Hh-Np from the secreting cell.
DR Reactome; R-DRE-8957275; Post-translational protein phosphorylation.
DR PRO; PR:C5H5C4; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 3.
DR Bgee; ENSDARG00000031126; Expressed in gastrula and 19 other tissues.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:1990699; F:palmitoleyl hydrolase activity; ISS:UniProtKB.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IMP:ZFIN.
DR GO; GO:0006507; P:GPI anchor release; IDA:ZFIN.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IDA:ZFIN.
DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; ISS:UniProtKB.
DR GO; GO:0021532; P:neural tube patterning; IMP:ZFIN.
DR GO; GO:1990697; P:protein depalmitoleylation; ISS:UniProtKB.
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 2: Evidence at transcript level;
KW Glycoprotein; Hydrolase; Reference proteome; Secreted; Serine esterase;
KW Signal; Wnt signaling pathway.
FT SIGNAL 1..26
FT /evidence="ECO:0000255"
FT CHAIN 27..500
FT /note="Palmitoleoyl-protein carboxylesterase notum1a"
FT /id="PRO_0000432991"
FT ACT_SITE 237
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:Q6P988"
FT ACT_SITE 344
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:Q6P988"
FT ACT_SITE 393
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:Q6P988"
FT CARBOHYD 101
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 500 AA; 56715 MW; 27C5BD9F717C1083 CRC64;
MKRSLWVMQV LHWAVMLALV QCGALGARRF RGGRNPQPRR ALPSAHYRDR GETTESFSLD
FTAVEENMDN FMTQVKNLAQ SLYPCSAQKL DYDMKLHFLE NTSVTCNDGT PAGYYLKESK
GSKRWLIFLE GGWYCFNKEN CDSRYETMRR LMSSSKWPQT KTGTGMLSSL PEENPHWWNA
NMVFIPYCSS DVWSGASPKT DQNDYAFMGS LIIKEVVKDL LSKGLDNAKI LLLAGSSAGG
TGVLLNVDSV SELLEELGHT NIQVRGLSDS GWFLDNKQYR CTDCVDTINC APTEVIKRGI
KYWGGVVPER CRQAYEGKEW NCFFGYKVYP TIKRPVFIVQ WLFDEAQLTV DNIHLTGQPV
QEGQWRYIQN LGTELRNTLK DVPAMFAPAC LSHEFITRNY WTDVQVKGTS LPRALHCWDR
SLQDTSRNNK SPPKGCPVHL IDSCPWPHCN PTCPTIRDQS TGQEMNVIQF LMHMGFDVQK
MAHQQGMDPS KLLGMLSSGS
