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NEUR1_HUMAN
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   03-AUG-2022, entry version 215.
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-C0;
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; 96.
DR   CORUM; Q99519; -.
DR   IntAct; Q99519; 30.
DR   MINT; Q99519; -.
DR   STRING; 9606.ENSP00000364782; -.
DR   BindingDB; Q99519; -.
DR   ChEMBL; CHEMBL2726; -.
DR   DrugBank; DB00945; Acetylsalicylic acid.
DR   DrugBank; DB00198; Oseltamivir.
DR   CAZy; GH33; Glycoside Hydrolase Family 33.
DR   GlyConnect; 1743; 2 N-Linked glycans (1 site).
DR   GlyGen; Q99519; 3 sites, 1 N-linked glycan (1 site).
DR   iPTMnet; Q99519; -.
DR   PhosphoSitePlus; Q99519; -.
DR   BioMuta; NEU1; -.
DR   DMDM; 17368612; -.
DR   EPD; Q99519; -.
DR   jPOST; Q99519; -.
DR   MassIVE; Q99519; -.
DR   MaxQB; Q99519; -.
DR   PaxDb; Q99519; -.
DR   PeptideAtlas; Q99519; -.
DR   PRIDE; Q99519; -.
DR   ProteomicsDB; 78308; -.
DR   Antibodypedia; 51599; 387 antibodies from 26 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   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; WSPTEFI; -.
DR   OrthoDB; 652179at2759; -.
DR   PhylomeDB; Q99519; -.
DR   TreeFam; TF331063; -.
DR   BRENDA; 3.2.1.18; 2681.
DR   PathwayCommons; Q99519; -.
DR   Reactome; R-HSA-1660662; Glycosphingolipid metabolism.
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   SABIO-RK; Q99519; -.
DR   SignaLink; Q99519; -.
DR   SIGNOR; Q99519; -.
DR   BioGRID-ORCS; 4758; 14 hits in 1082 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 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   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;
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
 
 
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