NEUR3_RAT
ID NEUR3_RAT Reviewed; 418 AA.
AC Q99PW5; Q497C0;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Sialidase-3;
DE EC=3.2.1.18 {ECO:0000250|UniProtKB:Q9UQ49};
DE AltName: Full=Ganglioside sialidase;
DE AltName: Full=Membrane sialidase;
DE AltName: Full=N-acetyl-alpha-neuraminidase 3;
GN Name=Neu3;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=11162581; DOI=10.1006/bbrc.2000.4186;
RA Hasegawa T., Feijoo Carnero C., Wada T., Itoyama Y., Miyagi T.;
RT "Differential expression of three sialidase genes in rat development.";
RL Biochem. Biophys. Res. Commun. 280:726-732(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
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).
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. 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. {ECO:0000250|UniProtKB:Q9UQ49}.
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:0000250|UniProtKB:Q9UQ49};
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:0000250|UniProtKB:Q9UQ49};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47833;
CC Evidence={ECO:0000250|UniProtKB:Q9UQ49};
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:0000250|UniProtKB:Q9UQ49};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47857;
CC Evidence={ECO:0000250|UniProtKB:Q9UQ49};
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:0000250|UniProtKB:Q9UQ49};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48121;
CC Evidence={ECO:0000250|UniProtKB:Q9UQ49};
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:0000250|UniProtKB:Q9UQ49};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48137;
CC Evidence={ECO:0000250|UniProtKB:Q9UQ49};
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:0000250|UniProtKB:Q9JMH7};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47873;
CC Evidence={ECO:0000250|UniProtKB:Q9JMH7};
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:0000250|UniProtKB:Q9JMH7};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48073;
CC Evidence={ECO:0000250|UniProtKB:Q9JMH7};
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:0000250|UniProtKB:Q9JMH7};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48069;
CC Evidence={ECO:0000250|UniProtKB:Q9JMH7};
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 -!- SUBUNIT: Interacts with CAV1; this interaction enhances NEU3 sialidase
CC activity within caveola. Interacts with EGFR; this interaction mediates
CC desialylation of EGFR enhancing downstream signaling.
CC {ECO:0000250|UniProtKB:Q9UQ49}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9UQ49};
CC Peripheral membrane protein {ECO:0000250|UniProtKB:Q9UQ49}. Membrane,
CC caveola {ECO:0000250|UniProtKB:Q9UQ49}. Early endosome membrane
CC {ECO:0000250|UniProtKB:Q9UQ49}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q9UQ49}. Recycling endosome membrane
CC {ECO:0000250|UniProtKB:Q9UQ49}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q9UQ49}. 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 (By similarity). S-acylated NEU3 likely
CC spans the lipid bilayer with a portion of C-terminus exposed to cytosol
CC and the catalytic region facing the extracellular space (By
CC similarity). {ECO:0000250|UniProtKB:Q9JMH7,
CC ECO:0000250|UniProtKB:Q9UQ49}.
CC -!- TISSUE SPECIFICITY: Expressed in brain, cardiac muscle and weakly in
CC liver. {ECO:0000269|PubMed:11162581}.
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; AB026841; BAB32440.1; -; mRNA.
DR EMBL; BC100625; AAI00626.1; -; mRNA.
DR PIR; JC7588; JC7588.
DR RefSeq; NP_446462.1; NM_054010.1.
DR RefSeq; XP_008757887.1; XM_008759665.2.
DR AlphaFoldDB; Q99PW5; -.
DR SMR; Q99PW5; -.
DR STRING; 10116.ENSRNOP00000024420; -.
DR CAZy; GH33; Glycoside Hydrolase Family 33.
DR PhosphoSitePlus; Q99PW5; -.
DR PaxDb; Q99PW5; -.
DR Ensembl; ENSRNOT00000024420; ENSRNOP00000024420; ENSRNOG00000018106.
DR GeneID; 117185; -.
DR KEGG; rno:117185; -.
DR UCSC; RGD:619881; rat.
DR CTD; 10825; -.
DR RGD; 619881; Neu3.
DR eggNOG; ENOG502QSFT; Eukaryota.
DR GeneTree; ENSGT00950000182944; -.
DR HOGENOM; CLU_024620_2_1_1; -.
DR InParanoid; Q99PW5; -.
DR OMA; YTYYIPY; -.
DR OrthoDB; 877888at2759; -.
DR PhylomeDB; Q99PW5; -.
DR TreeFam; TF331063; -.
DR Reactome; R-RNO-1660662; Glycosphingolipid metabolism.
DR Reactome; R-RNO-4085001; Sialic acid metabolism.
DR PRO; PR:Q99PW5; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000018106; Expressed in skeletal muscle tissue and 19 other tissues.
DR Genevisible; Q99PW5; RN.
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; ISO:RGD.
DR GO; GO:0009897; C:external side of plasma membrane; ISO:RGD.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0005765; C:lysosomal membrane; ISO:RGD.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0055038; C:recycling endosome membrane; ISO:RGD.
DR GO; GO:0016997; F:alpha-sialidase activity; ISO:RGD.
DR GO; GO:0052794; F:exo-alpha-(2->3)-sialidase activity; ISS: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:RGD.
DR GO; GO:0005975; P:carbohydrate metabolic process; ISO:RGD.
DR GO; GO:0006689; P:ganglioside catabolic process; ISS:UniProtKB.
DR GO; GO:1900186; P:negative regulation of clathrin-dependent endocytosis; ISO:RGD.
DR GO; GO:0009313; P:oligosaccharide catabolic process; ISO:RGD.
DR GO; GO:0045742; P:positive regulation of epidermal growth factor receptor signaling pathway; ISO:RGD.
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 2: Evidence at transcript level;
KW Carbohydrate metabolism; Cell membrane; Endosome; Glycosidase; Hydrolase;
KW Lipid degradation; Lipid metabolism; Lipoprotein; Lysosome; Membrane;
KW Reference proteome; Repeat.
FT CHAIN 1..418
FT /note="Sialidase-3"
FT /id="PRO_0000208905"
FT REPEAT 129..140
FT /note="BNR 1"
FT REPEAT 201..212
FT /note="BNR 2"
FT REPEAT 252..263
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"
SQ SEQUENCE 418 AA; 46980 MW; 7CC46F2E5952E240 CRC64;
MEEVSSCSLR STLFQQEEQN RITYRIPALL YIPPTHTFLA FAEMRTSSRD EDAVYLVFRR
GVMKGCSVEW GPQQPLMEAT LPGHRTMSPC PVWEKNTGRV YLFFICVQGH VSERWQLLWG
RNAARLCFLY SEDSGCSWGE VKDLTEEVVG SEMKHWATFA VGPGHGIQLQ SGRLLIPAYA
YLISCWFLCF PCSVKPHSLM FYSDDLGVTW HCGKFIKPQV TGECQVAEVP GKAGNLVLYC
SARTPNKFRA EAFSTDSGDC FQKPTLNQQL CEPRGGCQGS VVSTRPLKMP YTCQDSSGKD
VPSTQKCPLM DRSLEVEEGA GAPSGTWLLY SHPTNKKKRM NLGIYYNQNP LEVNYWSRPW
ILNRGPSGYS DLAVVEGQGL FACLFECGER HEDEKIDFCL FSDQEVLSCD DCTSPSSN
