ID   NEUR2_MOUSE             Reviewed;         379 AA.
AC   Q9JMH3; Q99NA3;
DT   16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2000, sequence version 1.
DT   24-JAN-2024, entry version 163.
DE   RecName: Full=Sialidase-2;
DE            EC=3.2.1.18 {ECO:0000269|PubMed:10329453, ECO:0000269|PubMed:10713120};
DE   AltName: Full=Cytosolic sialidase;
DE   AltName: Full=Mouse skeletal muscle sialidase;
DE            Short=MSS;
DE   AltName: Full=Murine thymic sialidase;
DE            Short=MTS;
DE   AltName: Full=N-acetyl-alpha-neuraminidase 2;
GN   Name=Neu2;
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], AND CATALYTIC ACTIVITY.
RC   TISSUE=Brain;
RX   PubMed=10329453; DOI=10.1006/bbrc.1999.0698;
RA   Fronda C.L., Zeng G., Gao L., Yu R.K.;
RT   "Molecular cloning and expression of mouse brain sialidase.";
RL   Biochem. Biophys. Res. Commun. 258:727-731(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, FUNCTION, AND CATALYTIC
RP   ACTIVITY.
RC   TISSUE=Skeletal muscle;
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   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Thymus;
RX   PubMed=11500029; DOI=10.1006/bbrc.2001.5374;
RA   Kotani K., Kuroiwa A., Saito T., Matsuda Y., Koda T., Kijimoto-Ochiai S.;
RT   "Cloning, chromosomal mapping, and characteristic 5'-UTR sequence of murine
RT   cytosolic sialidase.";
RL   Biochem. Biophys. Res. Commun. 286:250-258(2001).
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 (PubMed:10713120). Recognizes sialyl linkage positions
CC       of the glycan moiety as well as the supramolecular organization of the
CC       sialoglycoconjugate (By similarity). Displays preference for alpha-
CC       (2->3)-sialylated GD1a and GT1B gangliosides over alpha-(2->8)-
CC       sialylated GD1b, in both monomeric forms and micelles
CC       (PubMed:10713120). Hydrolyzes exclusively monomeric GM1 ganglioside,
CC       but has no activity toward the miscellar form (By similarity). Has
CC       lower sialidase activity for glycoproteins such as fetuin and
CC       TF/transferrin that carry a mixture of alpha-(2->3) and alpha-(2->6)-
CC       sialyl linkages (By similarity). Cleaves milk oligosaccharide alpha-
CC       (2->3)-sialyllactose, but is inactive toward isomer alpha-(2->6)-
CC       sialyllactose isomer. Has no activity toward colominic acid, a homomer
CC       of alpha-(2->8)-linked Neu5Ac residues (By similarity).
CC       {ECO:0000250|UniProtKB:Q9Y3R4, ECO:0000269|PubMed:10713120}.
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:10329453, ECO:0000269|PubMed:10713120};
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:10713120};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47833;
CC         Evidence={ECO:0000305|PubMed:10713120};
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:Q9Y3R4};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47873;
CC         Evidence={ECO:0000250|UniProtKB:Q9Y3R4};
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:0000250|UniProtKB:Q9Y3R4};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47829;
CC         Evidence={ECO:0000250|UniProtKB:Q9Y3R4};
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:0000250|UniProtKB:Q9Y3R4};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47877;
CC         Evidence={ECO:0000250|UniProtKB:Q9Y3R4};
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:10713120};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48121;
CC         Evidence={ECO:0000305|PubMed:10713120};
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:10713120};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48137;
CC         Evidence={ECO:0000305|PubMed:10713120};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a ganglioside GM2 + H2O = a ganglioside GA2 + N-
CC         acetylneuraminate; Xref=Rhea:RHEA:48172, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:35418, ChEBI:CHEBI:79218, ChEBI:CHEBI:90085;
CC         Evidence={ECO:0000269|PubMed:10713120};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48173;
CC         Evidence={ECO:0000305|PubMed:10713120};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a neolactoside IV(3)-alpha-NeuAc-nLc4Cer(d18:1(4E)) + H2O = a
CC         neolactoside nLc4Cer(d18:1(4E)) + N-acetylneuraminate;
CC         Xref=Rhea:RHEA:47852, ChEBI:CHEBI:15377, ChEBI:CHEBI:17006,
CC         ChEBI:CHEBI:35418, ChEBI:CHEBI:58665;
CC         Evidence={ECO:0000250|UniProtKB:Q9Y3R4};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47853;
CC         Evidence={ECO:0000250|UniProtKB:Q9Y3R4};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + N-acetyl-alpha-neuraminosyl-(2->3)-beta-D-galactosyl-
CC         (1->4)-D-glucose = lactose + N-acetylneuraminate;
CC         Xref=Rhea:RHEA:64640, ChEBI:CHEBI:15377, ChEBI:CHEBI:17716,
CC         ChEBI:CHEBI:35418, ChEBI:CHEBI:156068;
CC         Evidence={ECO:0000250|UniProtKB:Q9Y3R4};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64641;
CC         Evidence={ECO:0000250|UniProtKB:Q9Y3R4};
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC       {ECO:0000250|UniProtKB:Q9Y3R4}.
CC   -!- TISSUE SPECIFICITY: Highly expressed in heart.
CC       {ECO:0000269|PubMed:10713120}.
CC   -!- SIMILARITY: Belongs to the glycosyl hydrolase 33 family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAB39152.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; AF139059; -; NOT_ANNOTATED_CDS; mRNA.
DR   EMBL; AB028023; BAA92867.1; -; mRNA.
DR   EMBL; AB048604; BAB39152.1; ALT_INIT; mRNA.
DR   CCDS; CCDS15135.1; -.
DR   CCDS; CCDS48308.1; -.
DR   CCDS; CCDS48309.1; -.
DR   RefSeq; NP_001153635.1; NM_001160163.1.
DR   RefSeq; NP_001153636.1; NM_001160164.1.
DR   RefSeq; NP_001153637.1; NM_001160165.1.
DR   RefSeq; NP_056565.1; NM_015750.3.
DR   RefSeq; XP_006529587.1; XM_006529524.3.
DR   AlphaFoldDB; Q9JMH3; -.
DR   SMR; Q9JMH3; -.
DR   BioGRID; 204817; 2.
DR   STRING; 10090.ENSMUSP00000131409; -.
DR   ChEMBL; CHEMBL4296071; -.
DR   CAZy; GH33; Glycoside Hydrolase Family 33.
DR   iPTMnet; Q9JMH3; -.
DR   PhosphoSitePlus; Q9JMH3; -.
DR   MaxQB; Q9JMH3; -.
DR   PaxDb; 10090-ENSMUSP00000127913; -.
DR   ProteomicsDB; 287389; -.
DR   Antibodypedia; 34447; 310 antibodies from 27 providers.
DR   DNASU; 23956; -.
DR   Ensembl; ENSMUST00000070898.6; ENSMUSP00000065439.6; ENSMUSG00000079434.9.
DR   Ensembl; ENSMUST00000165109.2; ENSMUSP00000126509.2; ENSMUSG00000079434.9.
DR   Ensembl; ENSMUST00000166259.8; ENSMUSP00000132513.2; ENSMUSG00000079434.9.
DR   GeneID; 23956; -.
DR   KEGG; mmu:23956; -.
DR   UCSC; uc007bxa.2; mouse.
DR   AGR; MGI:1344417; -.
DR   CTD; 4759; -.
DR   MGI; MGI:1344417; Neu2.
DR   VEuPathDB; HostDB:ENSMUSG00000079434; -.
DR   eggNOG; ENOG502QSFT; Eukaryota.
DR   GeneTree; ENSGT00950000182944; -.
DR   HOGENOM; CLU_024620_2_1_1; -.
DR   InParanoid; Q9JMH3; -.
DR   OrthoDB; 5482010at2759; -.
DR   PhylomeDB; Q9JMH3; -.
DR   TreeFam; TF331063; -.
DR   Reactome; R-MMU-4085001; Sialic acid metabolism.
DR   Reactome; R-MMU-9840310; Glycosphingolipid catabolism.
DR   BioGRID-ORCS; 23956; 3 hits in 78 CRISPR screens.
DR   ChiTaRS; Neu2; mouse.
DR   PRO; PR:Q9JMH3; -.
DR   Proteomes; UP000000589; Chromosome 1.
DR   RNAct; Q9JMH3; Protein.
DR   Bgee; ENSMUSG00000079434; Expressed in temporalis muscle and 70 other cell types or tissues.
DR   ExpressionAtlas; Q9JMH3; baseline and differential.
DR   GO; GO:1902494; C:catalytic complex; ISO:MGI.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005829; C:cytosol; ISO:MGI.
DR   GO; GO:0005764; C:lysosome; IBA:GO_Central.
DR   GO; GO:0016020; C:membrane; IBA:GO_Central.
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; ISO:MGI.
DR   GO; GO:0006689; P:ganglioside catabolic process; IDA:UniProtKB.
DR   GO; GO:0006516; P:glycoprotein catabolic process; ISO:MGI.
DR   GO; GO:0009313; P:oligosaccharide catabolic process; IDA:UniProtKB.
DR   GO; GO:0045663; P:positive regulation of myoblast differentiation; ISO:MGI.
DR   GO; GO:0010831; P:positive regulation of myotube differentiation; ISO:MGI.
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:SF6; SIALIDASE-2; 1.
DR   Pfam; PF13088; BNR_2; 1.
DR   SUPFAM; SSF50939; Sialidases; 1.
DR   Genevisible; Q9JMH3; MM.
PE   1: Evidence at protein level;
KW   Carbohydrate metabolism; Cytoplasm; Glycosidase; Hydrolase;
KW   Lipid degradation; Lipid metabolism; Reference proteome; Repeat.
FT   CHAIN           1..379
FT                   /note="Sialidase-2"
FT                   /id="PRO_0000208900"
FT   REPEAT          127..138
FT                   /note="BNR 1"
FT   REPEAT          197..208
FT                   /note="BNR 2"
FT   MOTIF           20..23
FT                   /note="FRIP motif"
FT   ACT_SITE        46
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        303
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        333
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        354
FT                   /evidence="ECO:0000255"
FT   BINDING         21
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         41
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         218
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         237
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255"
FT   BINDING         303
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   CONFLICT        40
FT                   /note="K -> R (in Ref. 1; AF139059)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        91..97
FT                   /note="YDKQTKT -> MTSKKD (in Ref. 1; AF139059)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   379 AA;  42403 MW;  02124A46398F6793 CRC64;
     MATCPVLQKE TLFRTGVHAY RIPALLYLKK QKTLLAFAEK RASKTDEHAE LIVLRRGSYN
     EATNRVKWQP EEVVTQAQLE GHRSMNPCPL YDKQTKTLFL FFIAVPGRVS EHHQLHTKVN
     VTRLCCVSST DHGRTWSPIQ DLTETTIGST HQEWATFAVG PGHCLQLRNP AGSLLVPAYA
     YRKLHPAQKP TPFAFCFISL DHGHTWKLGN FVAENSLECQ VAEVGTGAQR MVYLNARSFL
     GARVQAQSPN DGLDFQDNRV VSKLVEPPHG CHGSVVAFHN PISKPHALDT WLLYTHPTDS
     RNRTNLGVYL NQMPLDPTAW SEPTLLAMGI CAYSDLQNMG QGPDGSPQFG CLYESGNYEE
     IIFLIFTLKQ AFPTVFDAQ
//