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   24-JAN-2024, entry version 122.
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=a ganglioside GD1a + H2O = a 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=a ganglioside GD1a (d18:1(4E)) + H2O = a 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=a ganglioside GD1b + H2O = a 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=a ganglioside GD1b (d18:1(4E)) + H2O = a 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=a ganglioside GD3 + H2O = a ganglioside GM3 + N-
CC         acetylneuraminate; Xref=Rhea:RHEA:48120, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:35418, 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=a ganglioside GD3 (d18:1(4E)) + H2O = a 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=a ganglioside GM3 + H2O = a 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=a ganglioside GM1 + H2O = a ganglioside GA1 + N-
CC         acetylneuraminate; Xref=Rhea:RHEA:47872, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:35418, 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=a ganglioside GM1 (d18:1(4E)) + H2O = a 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=a ganglioside GM2 (d18:1(4E)) + H2O = a 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=a ganglioside GM3 (d18:1(4E)) + H2O = a beta-D-Gal-(1->4)-
CC         beta-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=a ganglioside GT1b + H2O = a 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; 9913-ENSBTAP00000036593; -.
DR   GeneID; 281349; -.
DR   KEGG; bta:281349; -.
DR   CTD; 10825; -.
DR   eggNOG; ENOG502QSFT; Eukaryota.
DR   InParanoid; O97859; -.
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:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005764; C:lysosome; IBA:GO_Central.
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   CDD; cd15482; Sialidase_non-viral; 1.
DR   Gene3D; 2.120.10.10; -; 1.
DR   InterPro; IPR011040; Sialidase.
DR   InterPro; IPR026856; Sialidase_fam.
DR   InterPro; IPR036278; Sialidase_sf.
DR   PANTHER; PTHR10628; SIALIDASE; 1.
DR   PANTHER; PTHR10628:SF23; SIALIDASE-3; 1.
DR   Pfam; PF13088; BNR_2; 1.
DR   SUPFAM; SSF50939; Sialidases; 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
//