NEUR1_MOUSE
ID NEUR1_MOUSE Reviewed; 409 AA.
AC O35657; O55220; Q99KG9;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Sialidase-1;
DE EC=3.2.1.18;
DE AltName: Full=G9 sialidase;
DE AltName: Full=Lysosomal sialidase;
DE AltName: Full=N-acetyl-alpha-neuraminidase 1;
DE Flags: Precursor;
GN Name=Neu1; Synonyms=Neu;
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], CATALYTIC ACTIVITY, AND FUNCTION.
RC STRAIN=C57BL/RIJ;
RX PubMed=9363440; DOI=10.1093/glycob/7.7.975;
RA Carrillo M.B., Milner C.M., Ball S.T., Snoek M., Campbell R.D.;
RT "Cloning and characterization of a sialidase from the murine
RT histocompatibility-2 complex: low levels of mRNA and a single amino acid
RT mutation are responsible for reduced sialidase activity in mice carrying
RT the Neu1a allele.";
RL Glycobiology 7:975-986(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, FUNCTION, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J;
RX PubMed=9384611; DOI=10.1093/hmg/7.1.115;
RA Igdoura S.A., Gafuik C., Mertineit C., Saberi F., Pshezhetsky A.V.,
RA Potier M., Trasler J.M., Gravel R.A.;
RT "Cloning of the cDNA and gene encoding mouse lysosomal sialidase and
RT correction of sialidase deficiency in human sialidosis and mouse SM/J
RT fibroblasts.";
RL Hum. Mol. Genet. 7:115-121(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=129;
RX PubMed=14656967; DOI=10.1101/gr.1736803;
RA Xie T., Rowen L., Aguado B., Ahearn M.E., Madan A., Qin S., Campbell R.D.,
RA Hood L.;
RT "Analysis of the gene-dense major histocompatibility complex class III
RT region and its comparison to mouse.";
RL Genome Res. 13:2621-2636(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP VARIANT ILE-209.
RX PubMed=9425240; DOI=10.1093/hmg/7.2.313;
RA Rottier R.J., Bonten E.J., d'Azzo A.;
RT "A point mutation in the neu-1 locus causes the neuraminidase defect in the
RT SM/J mouse.";
RL Hum. Mol. Genet. 7:313-321(1998).
CC -!- FUNCTION: Catalyzes the removal of sialic acid (N-acetylneuraminic
CC acid) moieties from glycoproteins and glycolipids. To be active, it is
CC strictly dependent on its presence in the multienzyme complex. Appears
CC to have a preference for alpha 2-3 and alpha 2-6 sialyl linkage.
CC {ECO:0000269|PubMed:9363440, ECO:0000269|PubMed:9384611}.
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:9363440, ECO:0000269|PubMed:9384611};
CC -!- SUBUNIT: Interacts with cathepsin A (protective protein), beta-
CC galactosidase and N-acetylgalactosamine-6-sulfate sulfatase in a
CC multienzyme complex.
CC -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000269|PubMed:9384611};
CC Peripheral membrane protein {ECO:0000269|PubMed:9384611}; Lumenal side
CC {ECO:0000269|PubMed:9384611}. Lysosome lumen
CC {ECO:0000269|PubMed:9384611}. Cell membrane
CC {ECO:0000269|PubMed:9384611}. Cytoplasmic vesicle
CC {ECO:0000269|PubMed:9384611}. Note=Localized not only on the inner side
CC of the lysosomal membrane and in the lysosomal lumen, but also on the
CC plasma membrane and in intracellular vesicles.
CC -!- TISSUE SPECIFICITY: Highly expressed in kidney, epididymis, followed by
CC brain, spinal cord and weakly expressed in adrenal, heart, liver, lung
CC and spleen. {ECO:0000269|PubMed:9384611}.
CC -!- DOMAIN: A C-terminal internalization signal (YGTL) appears to allow the
CC targeting of plasma membrane proteins to endosomes.
CC -!- PTM: N-glycosylated. {ECO:0000305}.
CC -!- PTM: Phosphorylation of tyrosine within the internalization signal
CC results in inhibition of sialidase internalization and blockage on the
CC plasma membrane.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 33 family. {ECO:0000305}.
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DR EMBL; Y11412; CAA72215.1; -; mRNA.
DR EMBL; U93702; AAC53536.1; -; mRNA.
DR EMBL; AF109906; AAC84167.1; -; Genomic_DNA.
DR EMBL; BC004666; AAH04666.1; -; mRNA.
DR CCDS; CCDS28668.1; -.
DR RefSeq; NP_035023.3; NM_010893.3.
DR AlphaFoldDB; O35657; -.
DR SMR; O35657; -.
DR BioGRID; 201731; 1.
DR IntAct; O35657; 2.
DR STRING; 10090.ENSMUSP00000007253; -.
DR ChEMBL; CHEMBL4105926; -.
DR CAZy; GH33; Glycoside Hydrolase Family 33.
DR GlyConnect; 2710; 1 N-Linked glycan (1 site).
DR GlyGen; O35657; 4 sites, 1 N-linked glycan (1 site).
DR iPTMnet; O35657; -.
DR PhosphoSitePlus; O35657; -.
DR SwissPalm; O35657; -.
DR EPD; O35657; -.
DR PaxDb; O35657; -.
DR PeptideAtlas; O35657; -.
DR PRIDE; O35657; -.
DR ProteomicsDB; 287388; -.
DR Antibodypedia; 51599; 387 antibodies from 26 providers.
DR DNASU; 18010; -.
DR Ensembl; ENSMUST00000007253; ENSMUSP00000007253; ENSMUSG00000007038.
DR GeneID; 18010; -.
DR KEGG; mmu:18010; -.
DR UCSC; uc008cei.2; mouse.
DR CTD; 4758; -.
DR MGI; MGI:97305; Neu1.
DR VEuPathDB; HostDB:ENSMUSG00000007038; -.
DR eggNOG; ENOG502QSIT; Eukaryota.
DR GeneTree; ENSGT00950000182944; -.
DR HOGENOM; CLU_024620_3_0_1; -.
DR InParanoid; O35657; -.
DR OMA; WSPTEFI; -.
DR OrthoDB; 652179at2759; -.
DR PhylomeDB; O35657; -.
DR TreeFam; TF331063; -.
DR BRENDA; 3.2.1.18; 3474.
DR Reactome; R-MMU-1660662; Glycosphingolipid metabolism.
DR Reactome; R-MMU-4085001; Sialic acid metabolism.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR BioGRID-ORCS; 18010; 3 hits in 80 CRISPR screens.
DR ChiTaRS; Neu1; mouse.
DR PRO; PR:O35657; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; O35657; protein.
DR Bgee; ENSMUSG00000007038; Expressed in right kidney and 230 other tissues.
DR ExpressionAtlas; O35657; baseline and differential.
DR Genevisible; O35657; MM.
DR GO; GO:0030054; C:cell junction; ISO:MGI.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0043202; C:lysosomal lumen; IEA:UniProtKB-SubCell.
DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; IDA:MGI.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016997; F:alpha-sialidase activity; ISO:MGI.
DR GO; GO:0052794; F:exo-alpha-(2->3)-sialidase activity; IEA:UniProtKB-EC.
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; IEA:UniProtKB-EC.
DR GO; GO:0004308; F:exo-alpha-sialidase activity; IDA:MGI.
DR GO; GO:0006689; P:ganglioside catabolic process; IBA:GO_Central.
DR GO; GO:0009313; P:oligosaccharide catabolic process; ISS:UniProtKB.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISO:MGI.
DR GO; GO:2000291; P:regulation of myoblast proliferation; ISO:MGI.
DR InterPro; IPR011040; Sialidase.
DR InterPro; IPR026856; Sialidase_fam.
DR InterPro; IPR036278; Sialidase_sf.
DR PANTHER; PTHR10628; PTHR10628; 1.
DR Pfam; PF13088; BNR_2; 1.
DR SUPFAM; SSF50939; SSF50939; 1.
PE 1: Evidence at protein level;
KW Carbohydrate metabolism; Cell membrane; Cytoplasmic vesicle; Glycoprotein;
KW Glycosidase; Hydrolase; Lipid degradation; Lipid metabolism; Lysosome;
KW Membrane; Phosphoprotein; Reference proteome; Repeat; Signal.
FT SIGNAL 1..41
FT /evidence="ECO:0000255"
FT CHAIN 42..409
FT /note="Sialidase-1"
FT /id="PRO_0000012027"
FT REPEAT 106..117
FT /note="BNR 1"
FT REPEAT 166..177
FT /note="BNR 2"
FT REPEAT 225..236
FT /note="BNR 3"
FT REPEAT 341..352
FT /note="BNR 4"
FT MOTIF 71..74
FT /note="FRIP motif"
FT MOTIF 406..409
FT /note="Internalization signal"
FT ACT_SITE 97
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT ACT_SITE 258
FT /evidence="ECO:0000255"
FT ACT_SITE 364
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT ACT_SITE 388
FT /evidence="ECO:0000255"
FT BINDING 72
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 91
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 258
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 274
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 335
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT CARBOHYD 180
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 337
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 346
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 372
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 209
FT /note="L -> I (reduced activity)"
FT /evidence="ECO:0000269|PubMed:9425240"
FT CONFLICT 107
FT /note="R -> K (in Ref. 2; AAC53536)"
FT /evidence="ECO:0000305"
FT CONFLICT 113
FT /note="S -> C (in Ref. 2; AAC53536)"
FT /evidence="ECO:0000305"
FT CONFLICT 117..121
FT /note="STAFI -> PTGFM (in Ref. 2; AAC53536)"
FT /evidence="ECO:0000305"
FT CONFLICT 172..173
FT /note="GI -> AF (in Ref. 2; AAC53536)"
FT /evidence="ECO:0000305"
FT CONFLICT 344
FT /note="F -> L (in Ref. 2; AAC53536)"
FT /evidence="ECO:0000305"
FT CONFLICT 351
FT /note="Q -> L (in Ref. 4; AAH04666)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 409 AA; 44591 MW; 416BFD5BE27B8893 CRC64;
MVGADPTRPR GPLSYWAGRR GQGLAAIFLL LVSAAESEAR AEDDFSLVQP LVTMEQLLWV
SGKQIGSVDT FRIPLITATP RGTLLAFAEA RKKSASDEGA KFIAMRRSTD QGSTWSSTAF
IVDDGEASDG LNLGAVVNDV DTGIVFLIYT LCAHKVNCQV ASTMLVWSKD DGISWSPPRN
LSVDIGTEMF APGPGSGIQK QREPGKGRLI VCGHGTLERD GVFCLLSDDH GASWHYGTGV
SGIPFGQPKH DHDFNPDECQ PYELPDGSVI INARNQNNYH CRCRIVLRSY DACDTLRPRD
VTFDPELVDP VVAAGALATS SGIVFFSNPA HPEFRVNLTL RWSFSNGTSW QKERVQVWPG
PSGYSSLTAL ENSTDGKKQP PQLFVLYEKG LNRYTESISM VKISVYGTL
