NEUR2_MOUSE
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 03-AUG-2022, entry version 155.
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=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 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:Q9Y3R4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47873;
CC Evidence={ECO:0000250|UniProtKB:Q9Y3R4};
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:Q9Y3R4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47829;
CC Evidence={ECO:0000250|UniProtKB:Q9Y3R4};
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:Q9Y3R4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47877;
CC Evidence={ECO:0000250|UniProtKB:Q9Y3R4};
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 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 GM2 + H2O = N-acetyl-beta-D-galactosaminyl-(1->4)-
CC beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1<->1')-ceramide + 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 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.ENSMUSP00000127913; -.
DR ChEMBL; CHEMBL4296071; -.
DR CAZy; GH33; Glycoside Hydrolase Family 33.
DR iPTMnet; Q9JMH3; -.
DR PhosphoSitePlus; Q9JMH3; -.
DR MaxQB; Q9JMH3; -.
DR PaxDb; Q9JMH3; -.
DR PRIDE; Q9JMH3; -.
DR ProteomicsDB; 287389; -.
DR Antibodypedia; 34447; 270 antibodies from 27 providers.
DR DNASU; 23956; -.
DR Ensembl; ENSMUST00000070898; ENSMUSP00000065439; ENSMUSG00000079434.
DR Ensembl; ENSMUST00000165109; ENSMUSP00000126509; ENSMUSG00000079434.
DR Ensembl; ENSMUST00000166259; ENSMUSP00000132513; ENSMUSG00000079434.
DR GeneID; 23956; -.
DR KEGG; mmu:23956; -.
DR UCSC; uc007bxa.2; mouse.
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; 652179at2759; -.
DR PhylomeDB; Q9JMH3; -.
DR TreeFam; TF331063; -.
DR Reactome; R-MMU-1660662; Glycosphingolipid metabolism.
DR Reactome; R-MMU-4085001; Sialic acid metabolism.
DR BioGRID-ORCS; 23956; 3 hits in 73 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 68 other tissues.
DR ExpressionAtlas; Q9JMH3; baseline and differential.
DR Genevisible; Q9JMH3; MM.
DR GO; GO:1902494; C:catalytic complex; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; 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:0051692; P:cellular oligosaccharide catabolic process; 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 InterPro; IPR011040; Sialidase.
DR InterPro; IPR026945; Sialidase-2.
DR InterPro; IPR026856; Sialidase_fam.
DR InterPro; IPR036278; Sialidase_sf.
DR PANTHER; PTHR10628; PTHR10628; 1.
DR PANTHER; PTHR10628:SF6; PTHR10628:SF6; 1.
DR Pfam; PF13088; BNR_2; 1.
DR SUPFAM; SSF50939; SSF50939; 1.
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
