NEUR3_MOUSE
ID NEUR3_MOUSE Reviewed; 418 AA.
AC Q9JMH7;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Sialidase-3;
DE EC=3.2.1.18 {ECO:0000269|PubMed:10713120, ECO:0000269|PubMed:17708748};
DE AltName: Full=Ganglioside sialidase;
DE AltName: Full=Membrane sialidase;
DE AltName: Full=N-acetyl-alpha-neuraminidase 3;
GN Name=Neu3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=10713120; DOI=10.1074/jbc.275.11.8007;
RA Hasegawa T., Yamaguchi K., Wada T., Takeda A., Itoyama Y., Miyagi T.;
RT "Molecular cloning of mouse ganglioside sialidase and its increased
RT expression in Neuro2a cell differentiation.";
RL J. Biol. Chem. 275:8007-8015(2000).
RN [2]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=11696012; DOI=10.1042/0264-6021:3600233;
RA Li S.C., Li Y.T., Moriya S., Miyagi T.;
RT "Degradation of G(M1) and G(M2) by mammalian sialidases.";
RL Biochem. J. 360:233-237(2001).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP SUBCELLULAR LOCATION.
RX PubMed=14970224; DOI=10.1074/jbc.m400881200;
RA Papini N., Anastasia L., Tringali C., Croci G., Bresciani R., Yamaguchi K.,
RA Miyagi T., Preti A., Prinetti A., Prioni S., Sonnino S., Tettamanti G.,
RA Venerando B., Monti E.;
RT "The plasma membrane-associated sialidase MmNEU3 modifies the ganglioside
RT pattern of adjacent cells supporting its involvement in cell-to-cell
RT interactions.";
RL J. Biol. Chem. 279:16989-16995(2004).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-312, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=17708748; DOI=10.1042/bj20070503;
RA Zanchetti G., Colombi P., Manzoni M., Anastasia L., Caimi L., Borsani G.,
RA Venerando B., Tettamanti G., Preti A., Monti E., Bresciani R.;
RT "Sialidase NEU3 is a peripheral membrane protein localized on the cell
RT surface and in endosomal structures.";
RL Biochem. J. 408:211-219(2007).
CC -!- FUNCTION: Exo-alpha-sialidase that catalyzes the hydrolytic cleavage of
CC the terminal sialic acid (N-acetylneuraminic acid, Neu5Ac) of a glycan
CC moiety in the catabolism of glycolipids, glycoproteins and
CC oligosacharides. Displays high catalytic efficiency for gangliosides
CC including alpha-(2->3)-sialylated GD1a and GM3 and alpha-(2->8)-
CC sialylated GD3 (PubMed:17708748, PubMed:10713120, PubMed:11696012,
CC PubMed:14970224). Plays a role in the regulation of transmembrane
CC signaling through the modulation of ganglioside content of the lipid
CC bilayer and by direct interaction with signaling receptors, such as
CC EGFR. Desialylates EGFR and activates downstream signaling in
CC proliferating cells. Contributes to clathrin-mediated endocytosis by
CC regulating sorting of endocytosed receptors to early and recycling
CC endosomes (By similarity). {ECO:0000250|UniProtKB:Q9UQ49,
CC ECO:0000269|PubMed:10713120, ECO:0000269|PubMed:11696012,
CC ECO:0000269|PubMed:17708748}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolysis of alpha-(2->3)-, alpha-(2->6)-, alpha-
CC (2->8)- glycosidic linkages of terminal sialic acid residues in
CC oligosaccharides, glycoproteins, glycolipids, colominic acid and
CC synthetic substrates.; EC=3.2.1.18;
CC Evidence={ECO:0000269|PubMed:10713120, ECO:0000269|PubMed:17708748};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ganglioside GD1a + H2O = ganglioside GM1 + N-
CC acetylneuraminate; Xref=Rhea:RHEA:47832, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:35418, ChEBI:CHEBI:82637, ChEBI:CHEBI:82639;
CC Evidence={ECO:0000269|PubMed:10713120};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47833;
CC Evidence={ECO:0000305|PubMed:10713120};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ganglioside GD1a (d18:1(4E)) + H2O = ganglioside GM1
CC (d18:1(4E)) + N-acetylneuraminate; Xref=Rhea:RHEA:47856,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:35418, ChEBI:CHEBI:77709,
CC ChEBI:CHEBI:78445; Evidence={ECO:0000269|PubMed:14970224,
CC ECO:0000269|PubMed:17708748};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47857;
CC Evidence={ECO:0000305|PubMed:14970224, ECO:0000305|PubMed:17708748};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ganglioside GD1b + H2O = ganglioside GM1 + N-
CC acetylneuraminate; Xref=Rhea:RHEA:47876, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:35418, ChEBI:CHEBI:82639, ChEBI:CHEBI:82939;
CC Evidence={ECO:0000250|UniProtKB:Q9UQ49};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47877;
CC Evidence={ECO:0000250|UniProtKB:Q9UQ49};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ganglioside GD1b (d18:1(4E)) + H2O = ganglioside GM1
CC (d18:1(4E)) + N-acetylneuraminate; Xref=Rhea:RHEA:48064,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:35418, ChEBI:CHEBI:77709,
CC ChEBI:CHEBI:87785; Evidence={ECO:0000250|UniProtKB:Q9UQ49};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48065;
CC Evidence={ECO:0000250|UniProtKB:Q9UQ49};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ganglioside GD3 + H2O = ganglioside GM3 + N-acetylneuraminate;
CC Xref=Rhea:RHEA:48120, ChEBI:CHEBI:15377, ChEBI:CHEBI:35418,
CC ChEBI:CHEBI:79210, ChEBI:CHEBI:79214;
CC Evidence={ECO:0000269|PubMed:10713120};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48121;
CC Evidence={ECO:0000305|PubMed:10713120};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ganglioside GD3 (d18:1(4E)) + H2O = ganglioside GM3
CC (d18:1(4E)) + N-acetylneuraminate; Xref=Rhea:RHEA:48124,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:35418, ChEBI:CHEBI:60065,
CC ChEBI:CHEBI:78436; Evidence={ECO:0000250|UniProtKB:Q9UQ49};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48125;
CC Evidence={ECO:0000250|UniProtKB:Q9UQ49};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ganglioside GM3 + H2O = beta-D-galactosyl-(1->4)-beta-D-
CC glucosyl-(1<->1)-ceramide + N-acetylneuraminate;
CC Xref=Rhea:RHEA:48136, ChEBI:CHEBI:15377, ChEBI:CHEBI:35418,
CC ChEBI:CHEBI:79208, ChEBI:CHEBI:79210;
CC Evidence={ECO:0000269|PubMed:10713120};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48137;
CC Evidence={ECO:0000305|PubMed:10713120};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ganglioside GM1 + H2O = ganglioside GA1 + N-acetylneuraminate;
CC Xref=Rhea:RHEA:47872, ChEBI:CHEBI:15377, ChEBI:CHEBI:35418,
CC ChEBI:CHEBI:82639, ChEBI:CHEBI:88069;
CC Evidence={ECO:0000269|PubMed:11696012};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47873;
CC Evidence={ECO:0000305|PubMed:11696012};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ganglioside GM1 (d18:1(4E)) + H2O = ganglioside GA1
CC (d18:1(4E)) + N-acetylneuraminate; Xref=Rhea:RHEA:48072,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:27938, ChEBI:CHEBI:35418,
CC ChEBI:CHEBI:77709; Evidence={ECO:0000305|PubMed:11696012};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48073;
CC Evidence={ECO:0000305|PubMed:11696012};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ganglioside GM2 (d18:1(4E)) + H2O = ganglioside GA2
CC (d18:1(4E)) + N-acetylneuraminate; Xref=Rhea:RHEA:48068,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:27731, ChEBI:CHEBI:35418,
CC ChEBI:CHEBI:71502; Evidence={ECO:0000269|PubMed:11696012};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48069;
CC Evidence={ECO:0000305|PubMed:11696012};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ganglioside GM3 (d18:1(4E)) + H2O = a beta-D-Gal-(1->4)-beta-
CC D-Glc-(1<->1)-Cer(d18:1(4E)) + N-acetylneuraminate;
CC Xref=Rhea:RHEA:47900, ChEBI:CHEBI:15377, ChEBI:CHEBI:17950,
CC ChEBI:CHEBI:35418, ChEBI:CHEBI:60065;
CC Evidence={ECO:0000250|UniProtKB:Q9UQ49};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47901;
CC Evidence={ECO:0000250|UniProtKB:Q9UQ49};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ganglioside GT1b + H2O = ganglioside GD1b + N-
CC acetylneuraminate; Xref=Rhea:RHEA:47828, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:35418, ChEBI:CHEBI:82939, ChEBI:CHEBI:82940;
CC Evidence={ECO:0000250|UniProtKB:O97859};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47829;
CC Evidence={ECO:0000250|UniProtKB:O97859};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 3.8. {ECO:0000269|PubMed:14970224};
CC -!- SUBUNIT: Interacts with CAV1; this interaction enhances NEU3 sialidase
CC activity within caveola. Interacts with EGFR; this interaction mediates
CC desialylation of EGFR and enhances downstream signaling.
CC {ECO:0000250|UniProtKB:Q9UQ49}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:14970224,
CC ECO:0000269|PubMed:17708748}; Peripheral membrane protein
CC {ECO:0000269|PubMed:17708748}. Membrane, caveola
CC {ECO:0000250|UniProtKB:Q9UQ49}. Early endosome membrane
CC {ECO:0000269|PubMed:17708748}; Peripheral membrane protein
CC {ECO:0000269|PubMed:17708748}. Recycling endosome membrane
CC {ECO:0000269|PubMed:17708748}; Peripheral membrane protein
CC {ECO:0000269|PubMed:17708748}. Lysosome membrane
CC {ECO:0000250|UniProtKB:Q9UQ49}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q9UQ49}. Note=Associates with the external
CC leaflet of the plasma membrane (PubMed:17708748). S-acylated NEU3
CC likely spans the lipid bilayer with a portion of C-terminus exposed to
CC cytosol and the catalytic region facing the extracellular space (By
CC similarity). {ECO:0000250|UniProtKB:Q9UQ49,
CC ECO:0000269|PubMed:17708748}.
CC -!- TISSUE SPECIFICITY: Expressed in heart, brain and cerebral cortex.
CC {ECO:0000269|PubMed:10713120}.
CC -!- PTM: Palmitoylated; may regulate intracellular trafficking and
CC anchorage to plasma membrane and endomembranes.
CC {ECO:0000250|UniProtKB:Q9UQ49}.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 33 family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB026842; BAA92868.1; -; mRNA.
DR CCDS; CCDS21489.1; -.
DR RefSeq; NP_057929.1; NM_016720.2.
DR AlphaFoldDB; Q9JMH7; -.
DR SMR; Q9JMH7; -.
DR STRING; 10090.ENSMUSP00000045222; -.
DR ChEMBL; CHEMBL4106181; -.
DR ChEMBL; CHEMBL4296071; -.
DR SwissLipids; SLP:000001371; -.
DR CAZy; GH33; Glycoside Hydrolase Family 33.
DR iPTMnet; Q9JMH7; -.
DR PhosphoSitePlus; Q9JMH7; -.
DR SwissPalm; Q9JMH7; -.
DR MaxQB; Q9JMH7; -.
DR PaxDb; Q9JMH7; -.
DR PRIDE; Q9JMH7; -.
DR ProteomicsDB; 287390; -.
DR Antibodypedia; 56317; 78 antibodies from 14 providers.
DR DNASU; 50877; -.
DR Ensembl; ENSMUST00000036331; ENSMUSP00000045222; ENSMUSG00000035239.
DR GeneID; 50877; -.
DR KEGG; mmu:50877; -.
DR UCSC; uc009imc.1; mouse.
DR CTD; 10825; -.
DR MGI; MGI:1355305; Neu3.
DR VEuPathDB; HostDB:ENSMUSG00000035239; -.
DR eggNOG; ENOG502QSFT; Eukaryota.
DR GeneTree; ENSGT00950000182944; -.
DR HOGENOM; CLU_024620_2_1_1; -.
DR InParanoid; Q9JMH7; -.
DR OMA; YTYYIPY; -.
DR OrthoDB; 877888at2759; -.
DR PhylomeDB; Q9JMH7; -.
DR TreeFam; TF331063; -.
DR Reactome; R-MMU-1660662; Glycosphingolipid metabolism.
DR Reactome; R-MMU-4085001; Sialic acid metabolism.
DR BioGRID-ORCS; 50877; 3 hits in 74 CRISPR screens.
DR PRO; PR:Q9JMH7; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q9JMH7; protein.
DR Bgee; ENSMUSG00000035239; Expressed in cumulus cell and 142 other tissues.
DR ExpressionAtlas; Q9JMH7; baseline and differential.
DR Genevisible; Q9JMH7; MM.
DR GO; GO:0005901; C:caveola; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0031901; C:early endosome membrane; IDA:UniProtKB.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0005765; C:lysosomal membrane; ISO:MGI.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0055038; C:recycling endosome membrane; IDA:UniProtKB.
DR GO; GO:0016997; F:alpha-sialidase activity; ISO:MGI.
DR GO; GO:0052794; F:exo-alpha-(2->3)-sialidase activity; IDA:UniProtKB.
DR GO; GO:0052795; F:exo-alpha-(2->6)-sialidase activity; IEA:UniProtKB-EC.
DR GO; GO:0052796; F:exo-alpha-(2->8)-sialidase activity; ISS:UniProtKB.
DR GO; GO:0004308; F:exo-alpha-sialidase activity; ISO:MGI.
DR GO; GO:0005975; P:carbohydrate metabolic process; ISO:MGI.
DR GO; GO:0006689; P:ganglioside catabolic process; IDA:UniProtKB.
DR GO; GO:1900186; P:negative regulation of clathrin-dependent endocytosis; ISO:MGI.
DR GO; GO:0009313; P:oligosaccharide catabolic process; ISO:MGI.
DR GO; GO:0045742; P:positive regulation of epidermal growth factor receptor signaling pathway; ISO:MGI.
DR InterPro; IPR011040; Sialidase.
DR InterPro; IPR026944; Sialidase-3.
DR InterPro; IPR026856; Sialidase_fam.
DR InterPro; IPR036278; Sialidase_sf.
DR PANTHER; PTHR10628; PTHR10628; 1.
DR PANTHER; PTHR10628:SF23; PTHR10628:SF23; 1.
DR Pfam; PF13088; BNR_2; 1.
DR SUPFAM; SSF50939; SSF50939; 1.
PE 1: Evidence at protein level;
KW Carbohydrate metabolism; Cell membrane; Endosome; Glycosidase; Hydrolase;
KW Lipid degradation; Lipid metabolism; Lipoprotein; Lysosome; Membrane;
KW Phosphoprotein; Reference proteome; Repeat.
FT CHAIN 1..418
FT /note="Sialidase-3"
FT /id="PRO_0000208904"
FT REPEAT 129..140
FT /note="BNR 1"
FT REPEAT 203..214
FT /note="BNR 2"
FT REPEAT 254..265
FT /note="BNR 3"
FT MOTIF 24..27
FT /note="FRIP motif"
FT ACT_SITE 50
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT ACT_SITE 369
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT ACT_SITE 386
FT /evidence="ECO:0000255"
FT BINDING 25
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 45
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 179
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 181
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 223
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 243
FT /ligand="substrate"
FT /evidence="ECO:0000255"
FT BINDING 339
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT MOD_RES 312
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
SQ SEQUENCE 418 AA; 46846 MW; 64853FC963FE7686 CRC64;
MEEVPPYSLS STLFQQEEQS GVTYRIPALL YLPPTHTFLA FAEKRTSVRD EDAACLVLRR
GLMKGRSVQW GPQRLLMEAT LPGHRTMNPC PVWEKNTGRV YLFFICVRGH VTERCQIVWG
KNAARLCFLC SEDAGCSWGE VKDLTEEVIG SEVKRWATFA VGPGHGIQLH SGRLIIPAYA
YYVSRWFLCF ACSVKPHSLM IYSDDFGVTW HHGKFIEPQV TGECQVAEVA GTAGNPVLYC
SARTPSRFRA EAFSTDSGGC FQKPTLNPQL HEPRTGCQGS VVSFRPLKMP NTYQDSIGKG
APATQKCPLL DSPLEVEKGA ETPSATWLLY SHPTSKRKRI NLGIYYNRNP LEVNCWSRPW
ILNRGPSGYS DLAVVEEQDL VACLFECGEK NEYERIDFCL FSDHEVLSCE DCTSPSSD
