NEUR3_HUMAN
ID NEUR3_HUMAN Reviewed; 428 AA.
AC Q9UQ49; A8K327; Q9NQE1;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Sialidase-3;
DE EC=3.2.1.18 {ECO:0000269|PubMed:10405317, ECO:0000269|PubMed:10861246, ECO:0000269|PubMed:11298736, ECO:0000269|PubMed:12011038, ECO:0000269|PubMed:15847605, ECO:0000269|PubMed:20511247};
DE AltName: Full=Ganglioside sialidasedis;
DE AltName: Full=Membrane sialidase;
DE AltName: Full=N-acetyl-alpha-neuraminidase 3;
GN Name=NEU3;
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] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RC TISSUE=Brain;
RX PubMed=10405317; DOI=10.1006/bbrc.1999.0973;
RA Wada T., Yoshikawa Y., Tokuyama S., Kuwabara M., Akita H., Miyagi T.;
RT "Cloning, expression, and chromosomal mapping of a human ganglioside
RT sialidase.";
RL Biochem. Biophys. Res. Commun. 261:21-27(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY,
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RC TISSUE=Skeletal muscle;
RX PubMed=10861246; DOI=10.1042/0264-6021:3490343;
RA Monti E., Bassi M.T., Papini N., Riboni M., Manzoni M., Venerando B.,
RA Croci G., Preti A., Ballabio A., Tettamanti G., Borsani G.;
RT "Identification and expression of NEU3, a novel human sialidase associated
RT to the plasma membrane.";
RL Biochem. J. 349:343-351(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Mammary gland;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
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 [7]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP MUTAGENESIS OF ARG-25; GLU-51; ASN-88; VAL-107; ARG-114; GLY-162 AND
RP TYR-370.
RX PubMed=11298736; DOI=10.1046/j.1432-1327.2001.02069.x;
RA Wang Y., Yamaguchi K., Shimada Y., Zhao X., Miyagi T.;
RT "Site-directed mutagenesis of human membrane-associated ganglioside
RT sialidase: identification of amino-acid residues contributing to substrate
RT specificity.";
RL Eur. J. Biochem. 268:2201-2208(2001).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, MUTAGENESIS OF TYR-181
RP AND PHE-187, AND INTERACTION WITH CAV1.
RX PubMed=12011038; DOI=10.1074/jbc.m110515200;
RA Wang Y., Yamaguchi K., Wada T., Hata K., Zhao X., Fujimoto T., Miyagi T.;
RT "A close association of the ganglioside-specific sialidase Neu3 with
RT caveolin in membrane microdomains.";
RL J. Biol. Chem. 277:26252-26259(2002).
RN [9]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=15847605; DOI=10.1042/bj20050017;
RA Yamaguchi K., Hata K., Koseki K., Shiozaki K., Akita H., Wada T.,
RA Moriya S., Miyagi T.;
RT "Evidence for mitochondrial localization of a novel human sialidase
RT (NEU4).";
RL Biochem. J. 390:85-93(2005).
RN [10]
RP SUBCELLULAR LOCATION.
RX PubMed=17708748; DOI=10.1042/bj20070503;
RA Zanchetti G., Colombi P., Manzoni M., Anastasia L., Caimi L., Borsani G.,
RA Venerando B., Tettamanti G., Preti A., Monti E., Bresciani R.;
RT "Sialidase NEU3 is a peripheral membrane protein localized on the cell
RT surface and in endosomal structures.";
RL Biochem. J. 408:211-219(2007).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH EGFR.
RX PubMed=17334392; DOI=10.1038/sj.onc.1210341;
RA Wada T., Hata K., Yamaguchi K., Shiozaki K., Koseki K., Moriya S.,
RA Miyagi T.;
RT "A crucial role of plasma membrane-associated sialidase in the survival of
RT human cancer cells.";
RL Oncogene 26:2483-2490(2007).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [13]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, BINDING SITES, AND MUTAGENESIS
RP OF ARG-45; ASP-50; TYR-179; TYR-181; GLU-225; ARG-245; ARG-340 AND TYR-370.
RX PubMed=20511247; DOI=10.1093/glycob/cwq077;
RA Albohy A., Li M.D., Zheng R.B., Zou C., Cairo C.W.;
RT "Insight into substrate recognition and catalysis by the human
RT neuraminidase 3 (NEU3) through molecular modeling and site-directed
RT mutagenesis.";
RL Glycobiology 20:1127-1138(2010).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [15]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=26251452; DOI=10.1042/bj20141550;
RA Rodriguez-Walker M., Vilcaes A.A., Garbarino-Pico E., Daniotti J.L.;
RT "Role of plasma-membrane-bound sialidase NEU3 in clathrin-mediated
RT endocytosis.";
RL Biochem. J. 470:131-144(2015).
RN [16]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF ASP-50 AND TYR-370.
RX PubMed=25922362; DOI=10.1093/glycob/cwv026;
RA Mozzi A., Forcella M., Riva A., Difrancesco C., Molinari F., Martin V.,
RA Papini N., Bernasconi B., Nonnis S., Tedeschi G., Mazzucchelli L.,
RA Monti E., Fusi P., Frattini M.;
RT "NEU3 activity enhances EGFR activation without affecting EGFR expression
RT and acts on its sialylation levels.";
RL Glycobiology 25:855-868(2015).
RN [17]
RP FUNCTION, SUBCELLULAR LOCATION, AND PALMITOYLATION.
RX PubMed=28646141; DOI=10.1038/s41598-017-04488-w;
RA Rodriguez-Walker M., Daniotti J.L.;
RT "Human Sialidase Neu3 is S-Acylated and Behaves Like an Integral Membrane
RT Protein.";
RL Sci. Rep. 7:4167-4167(2017).
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. Displays high catalytic efficiency for gangliosides
CC including alpha-(2->3)-sialylated GD1a and GM3 and alpha-(2->8)-
CC sialylated GD3 (PubMed:11298736, PubMed:15847605, PubMed:10861246,
CC PubMed:20511247, PubMed:28646141, PubMed:10405317, PubMed:12011038).
CC Plays a role in the regulation of transmembrane signaling through the
CC modulation of ganglioside content of the lipid bilayer and by direct
CC interaction with signaling receptors, such as EGFR (PubMed:17334392,
CC PubMed:25922362). Desialylates EGFR and activates downstream signaling
CC in proliferating cells (PubMed:25922362). Contributes to clathrin-
CC mediated endocytosis by regulating sorting of endocytosed receptors to
CC early and recycling endosomes (PubMed:26251452).
CC {ECO:0000269|PubMed:10405317, ECO:0000269|PubMed:10861246,
CC ECO:0000269|PubMed:11298736, ECO:0000269|PubMed:12011038,
CC ECO:0000269|PubMed:15847605, ECO:0000269|PubMed:17334392,
CC ECO:0000269|PubMed:20511247, ECO:0000269|PubMed:25922362,
CC ECO:0000269|PubMed:26251452, ECO:0000269|PubMed:28646141}.
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:10405317, ECO:0000269|PubMed:10861246,
CC ECO:0000269|PubMed:11298736, ECO:0000269|PubMed:12011038,
CC ECO:0000269|PubMed:15847605, ECO:0000269|PubMed:20511247};
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:10405317, ECO:0000269|PubMed:11298736,
CC ECO:0000269|PubMed:15847605, ECO:0000269|PubMed:25922362};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47833;
CC Evidence={ECO:0000305|PubMed:10405317, ECO:0000305|PubMed:11298736,
CC ECO:0000305|PubMed:15847605, ECO:0000305|PubMed:25922362};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ganglioside GD1a (d18:1(4E)) + H2O = ganglioside GM1
CC (d18:1(4E)) + N-acetylneuraminate; Xref=Rhea:RHEA:47856,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:35418, ChEBI:CHEBI:77709,
CC ChEBI:CHEBI:78445; Evidence={ECO:0000305|PubMed:10405317,
CC ECO:0000305|PubMed:11298736, ECO:0000305|PubMed:15847605};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47857;
CC Evidence={ECO:0000305|PubMed:10405317, ECO:0000305|PubMed:11298736,
CC ECO:0000305|PubMed:15847605};
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:0000269|PubMed:10405317};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47877;
CC Evidence={ECO:0000305|PubMed:10405317};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ganglioside GD1b (d18:1(4E)) + H2O = ganglioside GM1
CC (d18:1(4E)) + N-acetylneuraminate; Xref=Rhea:RHEA:48064,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:35418, ChEBI:CHEBI:77709,
CC ChEBI:CHEBI:87785; Evidence={ECO:0000305|PubMed:10405317};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48065;
CC Evidence={ECO:0000305|PubMed:10405317};
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:10405317, ECO:0000269|PubMed:11298736,
CC ECO:0000269|PubMed:15847605};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48121;
CC Evidence={ECO:0000305|PubMed:10405317, ECO:0000305|PubMed:11298736,
CC ECO:0000305|PubMed:15847605};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ganglioside GD3 (d18:1(4E)) + H2O = ganglioside GM3
CC (d18:1(4E)) + N-acetylneuraminate; Xref=Rhea:RHEA:48124,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:35418, ChEBI:CHEBI:60065,
CC ChEBI:CHEBI:78436; Evidence={ECO:0000305|PubMed:10405317,
CC ECO:0000305|PubMed:11298736, ECO:0000305|PubMed:15847605};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48125;
CC Evidence={ECO:0000305|PubMed:10405317, ECO:0000305|PubMed:11298736,
CC ECO:0000305|PubMed:15847605};
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:10405317, ECO:0000269|PubMed:15847605,
CC ECO:0000269|PubMed:17334392};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48137;
CC Evidence={ECO:0000305|PubMed:10405317, ECO:0000305|PubMed:15847605,
CC ECO:0000305|PubMed:17334392};
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:Q9JMH7};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47873;
CC Evidence={ECO:0000250|UniProtKB:Q9JMH7};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ganglioside GM1 (d18:1(4E)) + H2O = ganglioside GA1
CC (d18:1(4E)) + N-acetylneuraminate; Xref=Rhea:RHEA:48072,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:27938, ChEBI:CHEBI:35418,
CC ChEBI:CHEBI:77709; Evidence={ECO:0000250|UniProtKB:Q9JMH7};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48073;
CC Evidence={ECO:0000250|UniProtKB:Q9JMH7};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ganglioside GM2 (d18:1(4E)) + H2O = ganglioside GA2
CC (d18:1(4E)) + N-acetylneuraminate; Xref=Rhea:RHEA:48068,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:27731, ChEBI:CHEBI:35418,
CC ChEBI:CHEBI:71502; Evidence={ECO:0000250|UniProtKB:Q9JMH7};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48069;
CC Evidence={ECO:0000250|UniProtKB:Q9JMH7};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ganglioside GM3 (d18:1(4E)) + H2O = a beta-D-Gal-(1->4)-beta-
CC D-Glc-(1<->1)-Cer(d18:1(4E)) + N-acetylneuraminate;
CC Xref=Rhea:RHEA:47900, ChEBI:CHEBI:15377, ChEBI:CHEBI:17950,
CC ChEBI:CHEBI:35418, ChEBI:CHEBI:60065;
CC Evidence={ECO:0000269|PubMed:10405317, ECO:0000269|PubMed:11298736,
CC ECO:0000269|PubMed:15847605};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47901;
CC Evidence={ECO:0000305|PubMed:10405317, ECO:0000305|PubMed:11298736,
CC ECO:0000305|PubMed:15847605};
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:O97859};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47829;
CC Evidence={ECO:0000250|UniProtKB:O97859};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=47 uM for ganglioside GD1a {ECO:0000269|PubMed:11298736};
CC pH dependence:
CC Optimum pH is 4.5-6.5. {ECO:0000269|PubMed:10405317,
CC ECO:0000269|PubMed:11298736};
CC Temperature dependence:
CC Optimum temperature is 20 degrees Celsius.
CC {ECO:0000269|PubMed:11298736};
CC -!- SUBUNIT: Interacts with CAV1; this interaction enhances NEU3 sialidase
CC activity within caveola (PubMed:12011038). Interacts with EGFR; this
CC interaction mediates desialylation of EGFR and enhances downstream
CC signaling (PubMed:17334392). {ECO:0000269|PubMed:12011038,
CC ECO:0000269|PubMed:17334392}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10861246,
CC ECO:0000269|PubMed:17708748, ECO:0000269|PubMed:26251452,
CC ECO:0000269|PubMed:28646141}; Peripheral membrane protein
CC {ECO:0000269|PubMed:10861246, ECO:0000269|PubMed:17708748}. Membrane,
CC caveola {ECO:0000269|PubMed:12011038}. Early endosome membrane
CC {ECO:0000269|PubMed:26251452}; Peripheral membrane protein
CC {ECO:0000305|PubMed:26251452}. Recycling endosome membrane
CC {ECO:0000269|PubMed:26251452}; Peripheral membrane protein
CC {ECO:0000305|PubMed:26251452}. Lysosome membrane
CC {ECO:0000269|PubMed:26251452}; Peripheral membrane protein
CC {ECO:0000305|PubMed:26251452}. Note=Associates with the external
CC leaflet of the plasma membrane (By similarity). S-acylated NEU3 likely
CC spans the lipid bilayer with a portion of C-terminus exposed to the
CC cytosol and the catalytic region facing the extracellular space
CC (PubMed:28646141). {ECO:0000250|UniProtKB:Q9JMH7,
CC ECO:0000269|PubMed:28646141}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9UQ49-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UQ49-2; Sequence=VSP_054145;
CC -!- TISSUE SPECIFICITY: Highly expressed in skeletal muscle, testis,
CC adrenal gland and thymus, followed by pancreas, liver, heart and
CC thymus. Weakly expressed in kidney, placenta, brain and lung.
CC {ECO:0000269|PubMed:10861246}.
CC -!- PTM: Palmitoylated; may regulate intracellular trafficking and
CC anchorage to plasma membrane and endomembranes.
CC {ECO:0000269|PubMed:28646141}.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 33 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAB96131.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/NEU3ID44505ch11q13.html";
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DR EMBL; AB008185; BAA82611.1; -; mRNA.
DR EMBL; Y18563; CAB96131.1; ALT_INIT; mRNA.
DR EMBL; AK022450; BAG51074.1; -; mRNA.
DR EMBL; AK290442; BAF83131.1; -; mRNA.
DR EMBL; AP001992; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471076; EAW74953.1; -; Genomic_DNA.
DR EMBL; BC136397; AAI36398.1; -; mRNA.
DR EMBL; BC144059; AAI44060.1; -; mRNA.
DR CCDS; CCDS44682.1; -. [Q9UQ49-2]
DR RefSeq; NP_006647.3; NM_006656.5. [Q9UQ49-2]
DR AlphaFoldDB; Q9UQ49; -.
DR SMR; Q9UQ49; -.
DR BioGRID; 116038; 23.
DR IntAct; Q9UQ49; 2.
DR STRING; 9606.ENSP00000294064; -.
DR BindingDB; Q9UQ49; -.
DR ChEMBL; CHEMBL3046; -.
DR DrugCentral; Q9UQ49; -.
DR SwissLipids; SLP:000001372; -. [Q9UQ49-1]
DR CAZy; GH33; Glycoside Hydrolase Family 33.
DR iPTMnet; Q9UQ49; -.
DR PhosphoSitePlus; Q9UQ49; -.
DR SwissPalm; Q9UQ49; -.
DR BioMuta; NEU3; -.
DR DMDM; 17369720; -.
DR EPD; Q9UQ49; -.
DR jPOST; Q9UQ49; -.
DR MassIVE; Q9UQ49; -.
DR MaxQB; Q9UQ49; -.
DR PaxDb; Q9UQ49; -.
DR PeptideAtlas; Q9UQ49; -.
DR PRIDE; Q9UQ49; -.
DR ProteomicsDB; 1854; -.
DR ProteomicsDB; 85507; -. [Q9UQ49-1]
DR Antibodypedia; 56317; 78 antibodies from 14 providers.
DR DNASU; 10825; -.
DR Ensembl; ENST00000294064.9; ENSP00000294064.4; ENSG00000162139.10. [Q9UQ49-2]
DR Ensembl; ENST00000531509.5; ENSP00000432097.1; ENSG00000162139.10. [Q9UQ49-2]
DR GeneID; 10825; -.
DR KEGG; hsa:10825; -.
DR MANE-Select; ENST00000294064.9; ENSP00000294064.4; NM_006656.6; NP_006647.3. [Q9UQ49-2]
DR UCSC; uc001ovw.4; human. [Q9UQ49-1]
DR CTD; 10825; -.
DR DisGeNET; 10825; -.
DR GeneCards; NEU3; -.
DR HGNC; HGNC:7760; NEU3.
DR HPA; ENSG00000162139; Low tissue specificity.
DR MIM; 604617; gene.
DR neXtProt; NX_Q9UQ49; -.
DR OpenTargets; ENSG00000162139; -.
DR PharmGKB; PA31562; -.
DR VEuPathDB; HostDB:ENSG00000162139; -.
DR eggNOG; ENOG502QSFT; Eukaryota.
DR GeneTree; ENSGT00950000182944; -.
DR HOGENOM; CLU_024620_2_0_1; -.
DR InParanoid; Q9UQ49; -.
DR OMA; YTYYIPY; -.
DR PhylomeDB; Q9UQ49; -.
DR TreeFam; TF331063; -.
DR BRENDA; 3.2.1.18; 2681.
DR PathwayCommons; Q9UQ49; -.
DR Reactome; R-HSA-1660662; Glycosphingolipid metabolism.
DR Reactome; R-HSA-4085001; Sialic acid metabolism.
DR SABIO-RK; Q9UQ49; -.
DR SignaLink; Q9UQ49; -.
DR BioGRID-ORCS; 10825; 15 hits in 1078 CRISPR screens.
DR ChiTaRS; NEU3; human.
DR GeneWiki; NEU3; -.
DR GenomeRNAi; 10825; -.
DR Pharos; Q9UQ49; Tchem.
DR PRO; PR:Q9UQ49; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9UQ49; protein.
DR Bgee; ENSG00000162139; Expressed in skeletal muscle tissue of rectus abdominis and 139 other tissues.
DR ExpressionAtlas; Q9UQ49; baseline and differential.
DR Genevisible; Q9UQ49; HS.
DR GO; GO:0005901; C:caveola; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0031901; C:early endosome membrane; IDA:UniProtKB.
DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0055038; C:recycling endosome membrane; IDA:UniProtKB.
DR GO; GO:0016997; F:alpha-sialidase activity; IDA:MGI.
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; IDA:UniProtKB.
DR GO; GO:0005975; P:carbohydrate metabolic process; IDA:MGI.
DR GO; GO:0006689; P:ganglioside catabolic process; IDA:UniProtKB.
DR GO; GO:0006687; P:glycosphingolipid metabolic process; TAS:Reactome.
DR GO; GO:1900186; P:negative regulation of clathrin-dependent endocytosis; IDA:UniProtKB.
DR GO; GO:0009313; P:oligosaccharide catabolic process; IDA:UniProtKB.
DR GO; GO:0045742; P:positive regulation of epidermal growth factor receptor signaling pathway; IMP:UniProtKB.
DR InterPro; IPR011040; Sialidase.
DR InterPro; IPR026944; Sialidase-3.
DR InterPro; IPR026856; Sialidase_fam.
DR InterPro; IPR036278; Sialidase_sf.
DR PANTHER; PTHR10628; PTHR10628; 1.
DR PANTHER; PTHR10628:SF23; PTHR10628:SF23; 1.
DR Pfam; PF13088; BNR_2; 1.
DR SUPFAM; SSF50939; SSF50939; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Carbohydrate metabolism; Cell membrane; Endosome;
KW Glycosidase; Hydrolase; Lipid degradation; Lipid metabolism; Lipoprotein;
KW Lysosome; Membrane; Phosphoprotein; Reference proteome; Repeat.
FT CHAIN 1..428
FT /note="Sialidase-3"
FT /id="PRO_0000208903"
FT REPEAT 129..140
FT /note="BNR 1"
FT REPEAT 203..214
FT /note="BNR 2"
FT REPEAT 254..265
FT /note="BNR 3"
FT REGION 294..318
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 24..27
FT /note="FRIP motif"
FT COMPBIAS 298..316
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 50
FT /note="Proton acceptor"
FT /evidence="ECO:0000269|PubMed:20511247"
FT ACT_SITE 370
FT /note="Nucleophile"
FT /evidence="ECO:0000269|PubMed:20511247"
FT ACT_SITE 387
FT /evidence="ECO:0000255"
FT BINDING 25
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 45
FT /ligand="substrate"
FT /evidence="ECO:0000305"
FT BINDING 179
FT /ligand="substrate"
FT /evidence="ECO:0000305"
FT BINDING 181
FT /ligand="substrate"
FT /evidence="ECO:0000305"
FT BINDING 225
FT /ligand="substrate"
FT /evidence="ECO:0000305"
FT BINDING 245
FT /ligand="substrate"
FT /evidence="ECO:0000305"
FT BINDING 340
FT /ligand="substrate"
FT /evidence="ECO:0000305"
FT MOD_RES 313
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JMH7"
FT VAR_SEQ 1
FT /note="M -> MRPADLPPRPMEESPASSSAPTETEEPGSSAEVM (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_054145"
FT VARIANT 15
FT /note="R -> Q (in dbSNP:rs7115499)"
FT /id="VAR_055839"
FT MUTAGEN 25
FT /note="R->H: Loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:11298736"
FT MUTAGEN 45
FT /note="R->V: Loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:20511247"
FT MUTAGEN 50
FT /note="D->S,A: Nearly abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:20511247,
FT ECO:0000269|PubMed:25922362"
FT MUTAGEN 51
FT /note="E->D: Decreases enzyme activity."
FT /evidence="ECO:0000269|PubMed:11298736"
FT MUTAGEN 88
FT /note="N->D: Markedly decreases enzyme activity."
FT /evidence="ECO:0000269|PubMed:11298736"
FT MUTAGEN 107
FT /note="V->M: Markedly decreases enzyme activity."
FT /evidence="ECO:0000269|PubMed:11298736"
FT MUTAGEN 114
FT /note="R->Q: Decreases enzyme activity."
FT /evidence="ECO:0000269|PubMed:11298736"
FT MUTAGEN 162
FT /note="G->A: Markedly decreases enzyme activity."
FT /evidence="ECO:0000269|PubMed:11298736"
FT MUTAGEN 179
FT /note="Y->F: Loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:20511247"
FT MUTAGEN 181
FT /note="Y->A: Markedly decreases the recruitment within
FT caveola."
FT /evidence="ECO:0000269|PubMed:12011038"
FT MUTAGEN 181
FT /note="Y->F: Nearly abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:20511247"
FT MUTAGEN 187
FT /note="F->R: Decreases the recruitment within caveola."
FT /evidence="ECO:0000269|PubMed:12011038"
FT MUTAGEN 225
FT /note="E->S: Loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:20511247"
FT MUTAGEN 245
FT /note="R->A: Loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:20511247"
FT MUTAGEN 340
FT /note="R->A: Loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:20511247"
FT MUTAGEN 370
FT /note="Y->F,C: Loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:11298736,
FT ECO:0000269|PubMed:20511247, ECO:0000269|PubMed:25922362"
SQ SEQUENCE 428 AA; 48252 MW; 35D1DD9359A78C98 CRC64;
MEEVTTCSFN SPLFRQEDDR GITYRIPALL YIPPTHTFLA FAEKRSTRRD EDALHLVLRR
GLRIGQLVQW GPLKPLMEAT LPGHRTMNPC PVWEQKSGCV FLFFICVRGH VTERQQIVSG
RNAARLCFIY SQDAGCSWSE VRDLTEEVIG SELKHWATFA VGPGHGIQLQ SGRLVIPAYT
YYIPSWFFCF QLPCKTRPHS LMIYSDDLGV TWHHGRLIRP MVTVECEVAE VTGRAGHPVL
YCSARTPNRC RAEALSTDHG EGFQRLALSR QLCEPPHGCQ GSVVSFRPLE IPHRCQDSSS
KDAPTIQQSS PGSSLRLEEE AGTPSESWLL YSHPTSRKQR VDLGIYLNQT PLEAACWSRP
WILHCGPCGY SDLAALEEEG LFGCLFECGT KQECEQIAFR LFTHREILSH LQGDCTSPGR
NPSQFKSN
