ID NEUR1_HUMAN Reviewed; 415 AA.
AC Q99519;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 27-MAR-2024, entry version 224.
DE RecName: Full=Sialidase-1;
DE EC=3.2.1.18;
DE AltName: Full=Acetylneuraminyl hydrolase;
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=NANH;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, FUNCTION, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, GLYCOSYLATION, AND VARIANT TYPE II SIALIDOSIS
RP ARG-91.
RC TISSUE=Fibroblast;
RX PubMed=8985184; DOI=10.1101/gad.10.24.3156;
RA Bonten E.J., van der Spoel A., Fornerod M., Grosveld G., d'Azzo A.;
RT "Characterization of human lysosomal neuraminidase defines the molecular
RT basis of the metabolic storage disorder sialidosis.";
RL Genes Dev. 10:3156-3169(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Monocyte;
RX PubMed=9020182; DOI=10.1074/jbc.272.7.4549;
RA Milner C.M., Smith S.V., Carrillo M.B., Taylor G.L., Hollinshead M.,
RA Campbell R.D.;
RT "Identification of a sialidase encoded in the human major
RT histocompatibility complex.";
RL J. Biol. Chem. 272:4549-4558(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, TISSUE SPECIFICITY, AND
RP VARIANTS SIALIDOSIS TYR-260 AND PRO-363.
RC TISSUE=Fibroblast;
RX PubMed=9054950; DOI=10.1038/ng0397-316;
RA Pshezhetsky A.V., Richard C., Michaud L., Igdoura S.A., Wang S.,
RA Elsliger M.-A., Ou J., Leclerc D., Gravel R.A., Dallaire L., Potier M.;
RT "Cloning, expression and chromosomal mapping of human lysosomal sialidase
RT and characterization of mutations in sialidosis.";
RL Nat. Genet. 15:316-320(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Shiina S., Tamiya G., Oka A., Inoko H.;
RT "Homo sapiens 2,229,817bp genomic DNA of 6p21.3 HLA class I region.";
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Kidney;
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 [8]
RP PROTEIN SEQUENCE OF 48-55, AND GLYCOSYLATION.
RC TISSUE=Placenta;
RX PubMed=9480870; DOI=10.1042/bj3300641;
RA Vinogradova M.V., Michaud L., Mezentsev A.V., Lukong K.E., El-Alfy M.,
RA Morales C.R., Potier M., Pshezhetsky A.V.;
RT "Molecular mechanism of lysosomal sialidase deficiency in galactosialidosis
RT involves its rapid degradation.";
RL Biochem. J. 330:641-650(1998).
RN [9]
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF TYR-412; GLY-413 AND LEU-415.
RX PubMed=11571282; DOI=10.1074/jbc.m104547200;
RA Lukong K.E., Seyrantepe V., Landry K., Trudel S., Ahmad A., Gahl W.A.,
RA Lefrancois S., Morales C.R., Pshezhetsky A.V.;
RT "Intracellular distribution of lysosomal sialidase is controlled by the
RT internalization signal in its cytoplasmic tail.";
RL J. Biol. Chem. 276:46172-46181(2001).
RN [10]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-352.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP CHARACTERIZATION OF VARIANTS SIALIDOSIS VAL-68; GLY-182; ARG-227; TYR-260;
RP PHE-270; VAL-298; SER-328 AND PRO-363.
RX PubMed=10767332; DOI=10.1093/hmg/9.7.1075;
RA Lukong K.E., Elsliger M.-A., Chang Y., Richard C., Thomas G., Carey W.,
RA Tylki-Szymanska A., Czartoryska B., Buchholz T., Rodriguez Criado G.,
RA Palmeri S., Pshezhetsky A.V.;
RT "Characterization of the sialidase molecular defects in sialidosis patients
RT suggests the structural organization of the lysosomal multienzyme
RT complex.";
RL Hum. Mol. Genet. 9:1075-1085(2000).
RN [13]
RP VARIANTS SIALIDOSIS MET-54; VAL-68; ARG-91; GLY-182; ALA-219; ARG-227;
RP HIS-231; TYR-260; PRO-270; SER-294; VAL-298; SER-328; GLN-335; PRO-363;
RP CYS-370 AND HIS-TYR-400 INS.
RX PubMed=11063730; DOI=10.1093/hmg/9.18.2715;
RA Bonten E.J., Arts W.F., Beck M., Covanis A., Donati M.A., Parini R.,
RA Zammarchi E., d'Azzo A.;
RT "Novel mutations in lysosomal neuraminidase identify functional domains and
RT determine clinical severity in sialidosis.";
RL Hum. Mol. Genet. 9:2715-2725(2000).
RN [14]
RP VARIANTS SIALIDOSIS MET-217 AND ARG-243, AND CHARACTERIZATION OF VARIANTS
RP SIALIDOSIS MET-217 AND ARG-243.
RX PubMed=10944856; DOI=10.1007/s100380070034;
RA Naganawa Y., Itoh K., Shimmoto M., Takiguchi K., Doi H., Nishizawa Y.,
RA Kobayashi T., Kamei S., Lukong K.E., Pshezhetsky A.V., Sakuraba H.;
RT "Molecular and structural studies of Japanese patients with sialidosis type
RT 1.";
RL J. Hum. Genet. 45:241-249(2000).
RN [15]
RP VARIANTS SIALIDOSIS VAL-68; GLY-182; ARG-227; ARG-240; TYR-260; PHE-270;
RP VAL-298; SER-328 AND PRO-363, AND CHARACTERIZATION OF VARIANTS SIALIDOSIS
RP VAL-68; GLY-182; ARG-227; TYR-260; PHE-270; VAL-298; SER-328 AND PRO-363.
RX PubMed=11279074; DOI=10.1074/jbc.m100460200;
RA Lukong K.E., Landry K., Elsliger M.-A., Chang Y., Lefrancois S.,
RA Morales C.R., Pshezhetsky A.V.;
RT "Mutations in sialidosis impair sialidase binding to the lysosomal
RT multienzyme complex.";
RL J. Biol. Chem. 276:17286-17290(2001).
RN [16]
RP VARIANTS SIALIDOSIS LEU-80; ARG-240 AND SER-316.
RX PubMed=11829139; DOI=10.1007/s10038-002-8652-7;
RA Itoh K., Naganawa Y., Matsuzawa F., Aikawa S., Doi H., Sasagasako N.,
RA Yamada T., Kira J., Kobayashi T., Pshezhetsky A.V., Sakuraba H.;
RT "Novel missense mutations in the human lysosomal sialidase gene in
RT sialidosis patients and prediction of structural alterations of mutant
RT enzymes.";
RL J. Hum. Genet. 47:29-37(2002).
RN [17]
RP VARIANTS SIALIDOSIS PRO-225; VAL-298 AND GLY-341, CATALYTIC ACTIVITY,
RP SUBCELLULAR LOCATION, AND CHARACTERIZATION OF VARIANTS SIALIDOSIS PRO-225;
RP VAL-298 AND GLY-341.
RX PubMed=14695530; DOI=10.1002/humu.10278;
RA Pattison S., Pankarican M., Rupar C.A., Graham F.L., Igdoura S.A.;
RT "Five novel mutations in the lysosomal sialidase gene (NEU1) in type II
RT sialidosis patients and assessment of their impact on enzyme activity and
RT intracellular targeting using adenovirus-mediated expression.";
RL Hum. Mutat. 23:32-39(2004).
RN [18]
RP VARIANTS SIALIDOSIS MET-217; ARG-243 AND SER-294, VARIANTS ALA-88; PHE-90;
RP ALA-179; GLN-208; ALA-210; ALA-217; MET-222; ASN-234; SER-248; SER-252;
RP THR-279; ARG-351 AND GLN-357, CHARACTERIZATION OF VARIANTS ALA-88; PHE-90;
RP ALA-210; ALA-217; MET-222 AND ASN-234, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=25153125; DOI=10.1371/journal.pone.0104229;
RA Bonardi D., Ravasio V., Borsani G., d'Azzo A., Bresciani R., Monti E.,
RA Giacopuzzi E.;
RT "In silico identification of new putative pathogenic variants in the NEU1
RT sialidase gene affecting enzyme function and subcellular localization.";
RL PLoS ONE 9:E104229-E104229(2014).
RN [19]
RP VARIANT SIALIDOSIS GLY-182.
RX PubMed=33798445; DOI=10.1016/j.ajhg.2021.03.013;
RA Courage C., Oliver K.L., Park E.J., Cameron J.M., Grabinska K.A., Muona M.,
RA Canafoglia L., Gambardella A., Said E., Afawi Z., Baykan B., Brandt C.,
RA di Bonaventura C., Chew H.B., Criscuolo C., Dibbens L.M., Castellotti B.,
RA Riguzzi P., Labate A., Filla A., Giallonardo A.T., Berecki G.,
RA Jackson C.B., Joensuu T., Damiano J.A., Kivity S., Korczyn A., Palotie A.,
RA Striano P., Uccellini D., Giuliano L., Andermann E., Scheffer I.E.,
RA Michelucci R., Bahlo M., Franceschetti S., Sessa W.C., Berkovic S.F.,
RA Lehesjoki A.E.;
RT "Progressive myoclonus epilepsies-Residual unsolved cases have marked
RT genetic heterogeneity including dolichol-dependent protein glycosylation
RT pathway genes.";
RL Am. J. Hum. Genet. 108:722-738(2021).
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:25153125, ECO:0000269|PubMed:8985184}.
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:14695530, ECO:0000269|PubMed:8985184,
CC ECO:0000269|PubMed:9054950};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 4.6.;
CC -!- SUBUNIT: Interacts with cathepsin A (protective protein), beta-
CC galactosidase and N-acetylgalactosamine-6-sulfate sulfatase in a
CC multienzyme complex.
CC -!- INTERACTION:
CC Q99519; Q13520: AQP6; NbExp=3; IntAct=EBI-721517, EBI-13059134;
CC Q99519; P11912: CD79A; NbExp=3; IntAct=EBI-721517, EBI-7797864;
CC Q99519; Q8IU89: CERS3; NbExp=3; IntAct=EBI-721517, EBI-18202821;
CC Q99519; Q9HA82: CERS4; NbExp=3; IntAct=EBI-721517, EBI-2622997;
CC Q99519; O43889-2: CREB3; NbExp=3; IntAct=EBI-721517, EBI-625022;
CC Q99519; Q96BA8: CREB3L1; NbExp=5; IntAct=EBI-721517, EBI-6942903;
CC Q99519; Q15125: EBP; NbExp=3; IntAct=EBI-721517, EBI-3915253;
CC Q99519; Q9Y282: ERGIC3; NbExp=3; IntAct=EBI-721517, EBI-781551;
CC Q99519; Q8NBJ4: GOLM1; NbExp=3; IntAct=EBI-721517, EBI-712073;
CC Q99519; Q8TDT2: GPR152; NbExp=3; IntAct=EBI-721517, EBI-13345167;
CC Q99519; Q8TED1: GPX8; NbExp=3; IntAct=EBI-721517, EBI-11721746;
CC Q99519; Q8NBQ5: HSD17B11; NbExp=3; IntAct=EBI-721517, EBI-1052304;
CC Q99519; O14880: MGST3; NbExp=3; IntAct=EBI-721517, EBI-724754;
CC Q99519; P15941-11: MUC1; NbExp=3; IntAct=EBI-721517, EBI-17263240;
CC Q99519; Q14973: SLC10A1; NbExp=3; IntAct=EBI-721517, EBI-3923031;
CC Q99519; Q3KNW5: SLC10A6; NbExp=3; IntAct=EBI-721517, EBI-18159983;
CC Q99519; P54219-3: SLC18A1; NbExp=3; IntAct=EBI-721517, EBI-17595455;
CC Q99519; Q9NUM3: SLC39A9; NbExp=3; IntAct=EBI-721517, EBI-2823239;
CC Q99519; Q9NUH8: TMEM14B; NbExp=3; IntAct=EBI-721517, EBI-8638294;
CC -!- SUBCELLULAR LOCATION: Lysosome membrane; Peripheral membrane protein;
CC Lumenal side. Lysosome lumen. Cell membrane. Cytoplasmic vesicle.
CC Lysosome {ECO:0000269|PubMed:25153125}. Note=Localized not only on the
CC inner side of the lysosomal membrane and in the lysosomal lumen, but
CC also on the plasma membrane and in intracellular vesicles.
CC -!- TISSUE SPECIFICITY: Highly expressed in pancreas, followed by skeletal
CC muscle, kidney, placenta, heart, lung and liver. Weakly expressed in
CC brain. {ECO:0000269|PubMed:8985184, ECO:0000269|PubMed:9054950}.
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:0000269|PubMed:19159218,
CC ECO:0000269|PubMed:8985184, ECO:0000269|PubMed:9480870}.
CC -!- PTM: Phosphorylation of tyrosine within the internalization signal
CC results in inhibition of sialidase internalization and blockage on the
CC plasma membrane.
CC -!- DISEASE: Sialidosis (SIALIDOSIS) [MIM:256550]: Lysosomal storage
CC disease occurring as two types with various manifestations. Type 1
CC sialidosis (cherry red spot-myoclonus syndrome or normosomatic type) is
CC late-onset and it is characterized by the formation of cherry red
CC macular spots in childhood, progressive debilitating myoclonus,
CC insiduous visual loss and rarely ataxia. The diagnosis can be confirmed
CC by the screening of the urine for sialyloligosaccharides. Type 2
CC sialidosis (also known as dysmorphic type) occurs as several variants
CC of increasing severity with earlier age of onset. It is characterized
CC by the presence of abnormal somatic features including coarse facies
CC and dysostosis multiplex, vertebral deformities, intellectual
CC disability, cherry-red spot/myoclonus, sialuria, cytoplasmic
CC vacuolation of peripheral lymphocytes, bone marrow cells and
CC conjunctival epithelial cells. {ECO:0000269|PubMed:10767332,
CC ECO:0000269|PubMed:10944856, ECO:0000269|PubMed:11063730,
CC ECO:0000269|PubMed:11279074, ECO:0000269|PubMed:11829139,
CC ECO:0000269|PubMed:14695530, ECO:0000269|PubMed:25153125,
CC ECO:0000269|PubMed:33798445, ECO:0000269|PubMed:8985184,
CC ECO:0000269|PubMed:9054950}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 33 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Neuraminidase entry;
CC URL="https://en.wikipedia.org/wiki/Neuraminidase";
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DR EMBL; AF040958; AAB96774.1; -; mRNA.
DR EMBL; X78687; CAA55356.1; -; mRNA.
DR EMBL; U84246; AAD09239.1; -; mRNA.
DR EMBL; AF134726; AAD21814.1; -; Genomic_DNA.
DR EMBL; BA000025; BAB63297.1; -; Genomic_DNA.
DR EMBL; BT007206; AAP35870.1; -; mRNA.
DR EMBL; BC000722; AAH00722.1; -; mRNA.
DR EMBL; BC011900; AAH11900.1; -; mRNA.
DR CCDS; CCDS4723.1; -.
DR RefSeq; NP_000425.1; NM_000434.3.
DR AlphaFoldDB; Q99519; -.
DR SMR; Q99519; -.
DR BioGRID; 110831; 107.
DR CORUM; Q99519; -.
DR IntAct; Q99519; 32.
DR MINT; Q99519; -.
DR STRING; 9606.ENSP00000364782; -.
DR BindingDB; Q99519; -.
DR ChEMBL; CHEMBL2726; -.
DR DrugBank; DB00945; Acetylsalicylic acid.
DR DrugBank; DB00482; Celecoxib.
DR DrugBank; DB00198; Oseltamivir.
DR CAZy; GH33; Glycoside Hydrolase Family 33.
DR GlyConnect; 1743; 2 N-Linked glycans (1 site).
DR GlyCosmos; Q99519; 3 sites, 1 glycan.
DR GlyGen; Q99519; 3 sites, 1 N-linked glycan (1 site).
DR iPTMnet; Q99519; -.
DR PhosphoSitePlus; Q99519; -.
DR SwissPalm; Q99519; -.
DR BioMuta; NEU1; -.
DR DMDM; 17368612; -.
DR EPD; Q99519; -.
DR jPOST; Q99519; -.
DR MassIVE; Q99519; -.
DR MaxQB; Q99519; -.
DR PaxDb; 9606-ENSP00000364782; -.
DR PeptideAtlas; Q99519; -.
DR ProteomicsDB; 78308; -.
DR Pumba; Q99519; -.
DR Antibodypedia; 51599; 437 antibodies from 27 providers.
DR DNASU; 4758; -.
DR Ensembl; ENST00000229725.4; ENSP00000229725.4; ENSG00000184494.8.
DR Ensembl; ENST00000375631.5; ENSP00000364782.4; ENSG00000204386.12.
DR Ensembl; ENST00000411774.3; ENSP00000399309.3; ENSG00000234846.7.
DR Ensembl; ENST00000422978.2; ENSP00000408957.2; ENSG00000227129.6.
DR Ensembl; ENST00000423382.2; ENSP00000401067.2; ENSG00000228691.6.
DR Ensembl; ENST00000434496.2; ENSP00000409489.2; ENSG00000234343.6.
DR Ensembl; ENST00000437432.2; ENSP00000403720.2; ENSG00000223957.6.
DR Ensembl; ENST00000439648.2; ENSP00000408207.2; ENSG00000227315.7.
DR GeneID; 4758; -.
DR KEGG; hsa:4758; -.
DR MANE-Select; ENST00000375631.5; ENSP00000364782.4; NM_000434.4; NP_000425.1.
DR UCSC; uc003nxq.5; human.
DR AGR; HGNC:7758; -.
DR CTD; 4758; -.
DR DisGeNET; 4758; -.
DR GeneCards; NEU1; -.
DR HGNC; HGNC:7758; NEU1.
DR HPA; ENSG00000204386; Low tissue specificity.
DR MalaCards; NEU1; -.
DR MIM; 256550; phenotype.
DR MIM; 608272; gene.
DR neXtProt; NX_Q99519; -.
DR OpenTargets; ENSG00000204386; -.
DR Orphanet; 93400; Congenital sialidosis type 2.
DR Orphanet; 93399; Juvenile sialidosis type 2.
DR Orphanet; 812; Sialidosis type 1.
DR PharmGKB; PA31560; -.
DR VEuPathDB; HostDB:ENSG00000204386; -.
DR eggNOG; ENOG502QSIT; Eukaryota.
DR GeneTree; ENSGT00950000182944; -.
DR HOGENOM; CLU_024620_3_0_1; -.
DR InParanoid; Q99519; -.
DR OMA; IRSYDAC; -.
DR OrthoDB; 2900690at2759; -.
DR PhylomeDB; Q99519; -.
DR TreeFam; TF331063; -.
DR BRENDA; 3.2.1.18; 2681.
DR PathwayCommons; Q99519; -.
DR Reactome; R-HSA-4085001; Sialic acid metabolism.
DR Reactome; R-HSA-4341670; Defective NEU1 causes sialidosis.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-9840310; Glycosphingolipid catabolism.
DR SABIO-RK; Q99519; -.
DR SignaLink; Q99519; -.
DR SIGNOR; Q99519; -.
DR BioGRID-ORCS; 4758; 14 hits in 1166 CRISPR screens.
DR ChiTaRS; NEU1; human.
DR GeneWiki; NEU1; -.
DR GenomeRNAi; 4758; -.
DR Pharos; Q99519; Tchem.
DR PRO; PR:Q99519; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q99519; Protein.
DR Bgee; ENSG00000184494; Expressed in placenta and 4 other cell types or tissues.
DR ExpressionAtlas; Q99519; baseline and differential.
DR Genevisible; Q99519; HS.
DR GO; GO:0030054; C:cell junction; IDA:HPA.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0043202; C:lysosomal lumen; TAS:Reactome.
DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0035580; C:specific granule lumen; TAS:Reactome.
DR GO; GO:0016997; F:alpha-sialidase activity; IMP:UniProtKB.
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:UniProtKB.
DR GO; GO:0006689; P:ganglioside catabolic process; IBA:GO_Central.
DR GO; GO:0009313; P:oligosaccharide catabolic process; IMP:UniProtKB.
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:SF25; SIALIDASE-1; 1.
DR Pfam; PF13088; BNR_2; 1.
DR SUPFAM; SSF50939; Sialidases; 1.
PE 1: Evidence at protein level;
KW Carbohydrate metabolism; Cell membrane; Cytoplasmic vesicle;
KW Direct protein sequencing; Disease variant; Glycoprotein; Glycosidase;
KW Hydrolase; Lipid degradation; Lipid metabolism; Lysosome; Membrane;
KW Phosphoprotein; Reference proteome; Repeat; Signal.
FT SIGNAL 1..47
FT /evidence="ECO:0000269|PubMed:9480870"
FT CHAIN 48..415
FT /note="Sialidase-1"
FT /id="PRO_0000012026"
FT REPEAT 112..123
FT /note="BNR 1"
FT REPEAT 172..183
FT /note="BNR 2"
FT REPEAT 231..242
FT /note="BNR 3"
FT REPEAT 347..358
FT /note="BNR 4"
FT MOTIF 77..80
FT /note="FRIP motif"
FT MOTIF 412..415
FT /note="Internalization signal"
FT ACT_SITE 103
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT ACT_SITE 370
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT ACT_SITE 394
FT /evidence="ECO:0000255"
FT BINDING 78
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 97
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 264
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 280
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 341
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT CARBOHYD 186
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 343
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 352
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT VARIANT 54
FT /note="V -> M (in SIALIDOSIS; type 1; mild mutation as
FT residual activity is still measurable)"
FT /evidence="ECO:0000269|PubMed:11063730"
FT /id="VAR_012207"
FT VARIANT 68
FT /note="G -> V (in SIALIDOSIS; type 2; less than 10% of
FT activity)"
FT /evidence="ECO:0000269|PubMed:10767332,
FT ECO:0000269|PubMed:11063730, ECO:0000269|PubMed:11279074"
FT /id="VAR_012208"
FT VARIANT 80
FT /note="P -> L (in SIALIDOSIS; type 2; no enzyme activity;
FT retained in the endoplasmic reticulum / Golgi or rapidly
FT degraded in the lysosomes; dbSNP:rs104893985)"
FT /evidence="ECO:0000269|PubMed:11829139"
FT /id="VAR_017460"
FT VARIANT 88
FT /note="G -> A (does not affect sialidase activity;
FT dbSNP:rs34712643)"
FT /evidence="ECO:0000269|PubMed:25153125"
FT /id="VAR_049203"
FT VARIANT 90
FT /note="L -> F (does not affect sialidase activity;
FT dbSNP:rs374556080)"
FT /evidence="ECO:0000269|PubMed:25153125"
FT /id="VAR_079557"
FT VARIANT 91
FT /note="L -> R (in SIALIDOSIS; type 2; dbSNP:rs104893972)"
FT /evidence="ECO:0000269|PubMed:11063730,
FT ECO:0000269|PubMed:8985184"
FT /id="VAR_012209"
FT VARIANT 179
FT /note="V -> A (in dbSNP:rs150302766)"
FT /evidence="ECO:0000269|PubMed:25153125"
FT /id="VAR_079558"
FT VARIANT 182
FT /note="S -> G (in SIALIDOSIS; type 1; normally processed;
FT dbSNP:rs398123392)"
FT /evidence="ECO:0000269|PubMed:10767332,
FT ECO:0000269|PubMed:11063730, ECO:0000269|PubMed:11279074,
FT ECO:0000269|PubMed:33798445"
FT /id="VAR_012210"
FT VARIANT 208
FT /note="R -> Q (in dbSNP:rs375104221)"
FT /evidence="ECO:0000269|PubMed:25153125"
FT /id="VAR_079559"
FT VARIANT 210
FT /note="P -> A (does not affect sialidase activity;
FT dbSNP:rs151177689)"
FT /evidence="ECO:0000269|PubMed:25153125"
FT /id="VAR_079560"
FT VARIANT 217
FT /note="V -> A (significant decrease in sialidase activity;
FT absence of lysosomal localization; mislocalization to the
FT endoplasmic reticulum; dbSNP:rs146850952)"
FT /evidence="ECO:0000269|PubMed:25153125"
FT /id="VAR_079561"
FT VARIANT 217
FT /note="V -> M (in SIALIDOSIS; type 1; partial transport and
FT residual transport activity; dbSNP:rs28940583)"
FT /evidence="ECO:0000269|PubMed:10944856,
FT ECO:0000269|PubMed:25153125"
FT /id="VAR_012211"
FT VARIANT 219
FT /note="G -> A (in SIALIDOSIS; type 1; unable to reach the
FT lysosomes; dbSNP:rs754068739)"
FT /evidence="ECO:0000269|PubMed:11063730"
FT /id="VAR_012212"
FT VARIANT 222
FT /note="T -> M (does not affect sialidase activity;
FT dbSNP:rs201684013)"
FT /evidence="ECO:0000269|PubMed:25153125"
FT /id="VAR_079562"
FT VARIANT 225
FT /note="R -> P (in SIALIDOSIS; type 2; impaired enzyme
FT folding; dbSNP:rs104893980)"
FT /evidence="ECO:0000269|PubMed:14695530"
FT /id="VAR_018076"
FT VARIANT 227
FT /note="G -> R (in SIALIDOSIS; type 1 and juvenile type 2;
FT catalytically inactive; retained in pre-lysosomal
FT compartments; dbSNP:rs769765227)"
FT /evidence="ECO:0000269|PubMed:10767332,
FT ECO:0000269|PubMed:11063730, ECO:0000269|PubMed:11279074"
FT /id="VAR_012213"
FT VARIANT 231
FT /note="L -> H (in SIALIDOSIS; type 1; unable to reach the
FT lysosomes; dbSNP:rs762400331)"
FT /evidence="ECO:0000269|PubMed:11063730"
FT /id="VAR_012214"
FT VARIANT 234
FT /note="D -> N (significant decrease in sialidase activity;
FT absence of lysosomal localization; mislocalization to the
FT endoplasmic reticulum; dbSNP:rs143868999)"
FT /evidence="ECO:0000269|PubMed:25153125"
FT /id="VAR_079563"
FT VARIANT 240
FT /note="W -> R (in SIALIDOSIS; type 2; no enzyme activity;
FT retained in the endoplasmic reticulum / Golgi or rapidly
FT degraded in the lysosomes; dbSNP:rs104893978)"
FT /evidence="ECO:0000269|PubMed:11279074,
FT ECO:0000269|PubMed:11829139"
FT /id="VAR_012215"
FT VARIANT 243
FT /note="G -> R (in SIALIDOSIS; type 1; no enzyme activity
FT and no transport to the lysosome; dbSNP:rs104893983)"
FT /evidence="ECO:0000269|PubMed:10944856,
FT ECO:0000269|PubMed:25153125"
FT /id="VAR_012216"
FT VARIANT 248
FT /note="G -> S (in dbSNP:rs373311653)"
FT /evidence="ECO:0000269|PubMed:25153125"
FT /id="VAR_079564"
FT VARIANT 252
FT /note="G -> S (does not affect sialidase activity;
FT dbSNP:rs145177628)"
FT /evidence="ECO:0000269|PubMed:25153125"
FT /id="VAR_079565"
FT VARIANT 260
FT /note="F -> Y (in SIALIDOSIS; infantile type 2;
FT catalytically inactive; rapid intralysosomal degradation;
FT dbSNP:rs104893977)"
FT /evidence="ECO:0000269|PubMed:10767332,
FT ECO:0000269|PubMed:11063730, ECO:0000269|PubMed:11279074,
FT ECO:0000269|PubMed:9054950"
FT /id="VAR_012217"
FT VARIANT 270
FT /note="L -> F (in SIALIDOSIS; type 2; reduction in enzyme
FT activity; rapid intralysosomal degradation)"
FT /evidence="ECO:0000269|PubMed:10767332,
FT ECO:0000269|PubMed:11279074"
FT /id="VAR_012219"
FT VARIANT 270
FT /note="L -> P (in SIALIDOSIS)"
FT /evidence="ECO:0000269|PubMed:11063730"
FT /id="VAR_012218"
FT VARIANT 279
FT /note="A -> T (in dbSNP:rs368320390)"
FT /evidence="ECO:0000269|PubMed:25153125"
FT /id="VAR_079566"
FT VARIANT 294
FT /note="R -> S (in SIALIDOSIS; type 1; mild mutation as
FT residual activity is still measurable; dbSNP:rs190549838)"
FT /evidence="ECO:0000269|PubMed:11063730,
FT ECO:0000269|PubMed:25153125"
FT /id="VAR_012220"
FT VARIANT 298
FT /note="A -> V (in SIALIDOSIS; type 2; less than 10% of
FT activity; rapid intralysosomal degradation; impaired enzyme
FT folding; dbSNP:rs104893981)"
FT /evidence="ECO:0000269|PubMed:10767332,
FT ECO:0000269|PubMed:11063730, ECO:0000269|PubMed:11279074,
FT ECO:0000269|PubMed:14695530"
FT /id="VAR_012221"
FT VARIANT 316
FT /note="P -> S (in SIALIDOSIS; type 1; no enzyme activity;
FT retained in the endoplasmic reticulum / Golgi or rapidly
FT degraded in the lysosomes; dbSNP:rs104893979)"
FT /evidence="ECO:0000269|PubMed:11829139"
FT /id="VAR_017461"
FT VARIANT 328
FT /note="G -> S (in SIALIDOSIS; type 1; reduction in enzyme
FT activity; dbSNP:rs534846786)"
FT /evidence="ECO:0000269|PubMed:10767332,
FT ECO:0000269|PubMed:11063730, ECO:0000269|PubMed:11279074"
FT /id="VAR_012222"
FT VARIANT 335
FT /note="P -> Q (in SIALIDOSIS; type 2; unable to reach the
FT lysosomes; dbSNP:rs749996046)"
FT /evidence="ECO:0000269|PubMed:11063730"
FT /id="VAR_012223"
FT VARIANT 341
FT /note="R -> G (in SIALIDOSIS; type 2; affects substrate
FT binding or catalysis; dbSNP:rs751458617)"
FT /evidence="ECO:0000269|PubMed:14695530"
FT /id="VAR_018077"
FT VARIANT 351
FT /note="S -> R (does not affect sialidase activity;
FT dbSNP:rs377573360)"
FT /evidence="ECO:0000269|PubMed:25153125"
FT /id="VAR_079567"
FT VARIANT 357
FT /note="R -> Q (in dbSNP:rs139301823)"
FT /evidence="ECO:0000269|PubMed:25153125"
FT /id="VAR_079568"
FT VARIANT 363
FT /note="L -> P (in SIALIDOSIS; infantile type 2; unable to
FT reach the lysosomes; dbSNP:rs193922915)"
FT /evidence="ECO:0000269|PubMed:10767332,
FT ECO:0000269|PubMed:11063730, ECO:0000269|PubMed:11279074,
FT ECO:0000269|PubMed:9054950"
FT /id="VAR_012224"
FT VARIANT 370
FT /note="Y -> C (in SIALIDOSIS; infantile type 2;
FT catalytically inactive; dbSNP:rs1310267862)"
FT /evidence="ECO:0000269|PubMed:11063730"
FT /id="VAR_012225"
FT VARIANT 400
FT /note="Y -> YHY (in SIALIDOSIS; type 1; mild mutation as
FT residual activity is still measurable)"
FT /id="VAR_012226"
FT MUTAGEN 412
FT /note="Y->A: Correct sorting to the plasma membrane but no
FT endocytosis and internalization."
FT /evidence="ECO:0000269|PubMed:11571282"
FT MUTAGEN 413
FT /note="G->A: Correct sorting to the plasma membrane but no
FT endocytosis and internalization."
FT /evidence="ECO:0000269|PubMed:11571282"
FT MUTAGEN 415
FT /note="L->A: Correct sorting to the plasma membrane but no
FT endocytosis and internalization."
FT /evidence="ECO:0000269|PubMed:11571282"
SQ SEQUENCE 415 AA; 45467 MW; 360E60A256DEA07F CRC64;
MTGERPSTAL PDRRWGPRIL GFWGGCRVWV FAAIFLLLSL AASWSKAEND FGLVQPLVTM
EQLLWVSGRQ IGSVDTFRIP LITATPRGTL LAFAEARKMS SSDEGAKFIA LRRSMDQGST
WSPTAFIVND GDVPDGLNLG AVVSDVETGV VFLFYSLCAH KAGCQVASTM LVWSKDDGVS
WSTPRNLSLD IGTEVFAPGP GSGIQKQREP RKGRLIVCGH GTLERDGVFC LLSDDHGASW
RYGSGVSGIP YGQPKQENDF NPDECQPYEL PDGSVVINAR NQNNYHCHCR IVLRSYDACD
TLRPRDVTFD PELVDPVVAA GAVVTSSGIV FFSNPAHPEF RVNLTLRWSF SNGTSWRKET
VQLWPGPSGY SSLATLEGSM DGEEQAPQLY VLYEKGRNHY TESISVAKIS VYGTL
//
