NEUR3_BOVIN
ID NEUR3_BOVIN Reviewed; 428 AA.
AC O97859;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 116.
DE RecName: Full=Sialidase-3;
DE EC=3.2.1.18 {ECO:0000269|PubMed:9988745};
DE AltName: Full=Ganglioside sialidase;
DE AltName: Full=Membrane sialidase;
DE AltName: Full=N-acetyl-alpha-neuraminidase 3;
GN Name=NEU3;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, FUNCTION, CATALYTIC
RP ACTIVITY, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RC TISSUE=Brain;
RX PubMed=9988745; DOI=10.1074/jbc.274.8.5004;
RA Miyagi T., Wada T., Iwamatsu A., Hata K., Yoshikawa Y., Tokuyama S.,
RA Sawada M.;
RT "Molecular cloning and characterization of a plasma membrane-associated
RT sialidase specific for gangliosides.";
RL J. Biol. Chem. 274:5004-5011(1999).
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:9988745). Plays a role in the regulation of
CC transmembrane signaling through the modulation of ganglioside content
CC of the lipid bilayer and by direct interaction with signaling
CC receptors, such as EGFR. Desialylates EGFR and activates downstream
CC signaling in proliferating cells. Contributes to clathrin-mediated
CC endocytosis by regulating sorting of endocytosed receptors to early and
CC recycling endosomes (By similarity). {ECO:0000250|UniProtKB:Q9UQ49,
CC ECO:0000269|PubMed:9988745}.
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:9988745};
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:9988745};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47833;
CC Evidence={ECO:0000305|PubMed:9988745};
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:0000269|PubMed:9988745};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47877;
CC Evidence={ECO:0000305|PubMed:9988745};
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:9988745};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48121;
CC Evidence={ECO:0000305|PubMed:9988745};
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:9988745};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48137;
CC Evidence={ECO:0000305|PubMed:9988745};
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:0000269|PubMed:9988745};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47829;
CC Evidence={ECO:0000305|PubMed:9988745};
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:9988745};
CC Peripheral membrane protein {ECO:0000269|PubMed:9988745}. 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. {ECO:0000269|PubMed:9988745}.
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}.
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DR EMBL; AB008184; BAA75071.1; -; mRNA.
DR RefSeq; NP_776547.2; NM_174122.3.
DR AlphaFoldDB; O97859; -.
DR SMR; O97859; -.
DR STRING; 9913.ENSBTAP00000036593; -.
DR CAZy; GH33; Glycoside Hydrolase Family 33.
DR PaxDb; O97859; -.
DR PRIDE; O97859; -.
DR GeneID; 281349; -.
DR KEGG; bta:281349; -.
DR CTD; 10825; -.
DR eggNOG; ENOG502QSFT; Eukaryota.
DR InParanoid; O97859; -.
DR OrthoDB; 877888at2759; -.
DR BRENDA; 3.2.1.18; 908.
DR Proteomes; UP000009136; Unplaced.
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; IEA:UniProtKB-SubCell.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
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; IEA:UniProtKB-SubCell.
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; IDA:UniProtKB.
DR GO; GO:0004308; F:exo-alpha-sialidase activity; IBA:GO_Central.
DR GO; GO:0006689; P:ganglioside catabolic process; IDA:UniProtKB.
DR GO; GO:0009313; P:oligosaccharide catabolic process; IBA:GO_Central.
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; Direct protein sequencing;
KW Endosome; Glycosidase; Hydrolase; Lipid degradation; Lipid metabolism;
KW Lipoprotein; Lysosome; Membrane; Phosphoprotein; Reference proteome;
KW Repeat.
FT CHAIN 1..428
FT /note="Sialidase-3"
FT /id="PRO_0000208902"
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 371
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT ACT_SITE 388
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 225
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 245
FT /ligand="substrate"
FT /evidence="ECO:0000255"
FT BINDING 341
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT MOD_RES 314
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JMH7"
SQ SEQUENCE 428 AA; 47917 MW; 418B34F3245A8F21 CRC64;
MEEVTSCSFS SPLFQQEDKR GVTYRIPALI YVPPAHTFLA FAEKRSSSKD EDALHLVLRR
GLRTGQSVQW EPLKSLMKAT LPGHRTMNPC PVWERKSGYV YLFFICVQGH VTERQQIMSG
RNPARLCFIC SQDAGYSWSD VRDLTEEVIG PEVTHWATFA VGPGHGIQLQ SGRLIIPAYA
YYIPFWFFCF RLPYRARPHS LMIYSDDLGA TWHHGRLIKP MVTVECEVAE VIGKAGHPVL
YCSARTPNRH RAEALSIDHG ECFQKPVLSH QLCEPPHGCQ GSVVSFCPLE IPGGCQDLAG
EDAPAIQQSP LLCSSVRPEP EAGTLSESWL LYSHPTNKKR RVDLGIYLNQ SPLEAACWSR
PWILHCGPCG YSDLAALENE GLFGCLFECG TKQECEQIAF RLFTDREILS HVQGDCSTPG
MNSEPSKK
