NEUR4_HUMAN
ID NEUR4_HUMAN Reviewed; 484 AA.
AC Q8WWR8; A8K056; J3KNJ5; Q96D64;
DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 07-MAR-2006, sequence version 3.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Sialidase-4;
DE EC=3.2.1.18 {ECO:0000269|PubMed:14962670, ECO:0000269|PubMed:15213228, ECO:0000269|PubMed:15847605, ECO:0000269|PubMed:21521691};
DE AltName: Full=N-acetyl-alpha-neuraminidase 4;
GN Name=NEU4; ORFNames=LP5125;
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), TISSUE SPECIFICITY (ISOFORM 1),
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND VARIANT ARG-301.
RC TISSUE=Fibroblast;
RX PubMed=14962670; DOI=10.1016/j.ygeno.2003.08.019;
RA Monti E., Bassi M.T., Bresciani R., Civini S., Croci G.L., Papini N.,
RA Riboni M., Zanchetti G., Ballabio A., Preti A., Tettamanti G.,
RA Venerando B., Borsani G.;
RT "Molecular cloning and characterization of NEU4, the fourth member of the
RT human sialidase gene family.";
RL Genomics 83:445-453(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-301.
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ARG-301.
RX PubMed=15498874; DOI=10.1073/pnas.0404089101;
RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X.,
RA Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X.,
RA Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J.;
RT "Large-scale cDNA transfection screening for genes related to cancer
RT development and progression.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.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=Oligodendroglioma;
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, IDENTIFICATION BY MASS SPECTROMETRY, ALTERNATIVE SPLICING
RP (ISOFORM 2), CATALYTIC ACTIVITY, SUBCELLULAR LOCATION (ISOFORM 2), AND
RP GLYCOSYLATION (ISOFORM 2).
RX PubMed=15213228; DOI=10.1074/jbc.m404531200;
RA Seyrantepe V., Landry K., Trudel S., Hassan J.A., Morales C.R.,
RA Pshezhetsky A.V.;
RT "Neu4, a novel human lysosomal lumen sialidase, confers normal phenotype to
RT sialidosis and galactosialidosis cells.";
RL J. Biol. Chem. 279:37021-37029(2004).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY (ISOFORMS 1 AND 2),
RP SUBCELLULAR LOCATION (ISOFORMS 1 AND 2), AND MUTAGENESIS OF ARG-5.
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 [9]
RP INDUCTION.
RX PubMed=15885103; DOI=10.1111/j.1742-4658.2005.04679.x;
RA Stamatos N.M., Liang F., Nan X., Landry K., Cross A.S., Wang L.X.,
RA Pshezhetsky A.V.;
RT "Differential expression of endogenous sialidases of human monocytes during
RT cellular differentiation into macrophages.";
RL FEBS J. 272:2545-2556(2005).
RN [10]
RP SUBCELLULAR LOCATION (ISOFORMS 1 AND 2).
RX PubMed=19797320; DOI=10.1093/glycob/cwp156;
RA Bigi A., Morosi L., Pozzi C., Forcella M., Tettamanti G., Venerando B.,
RA Monti E., Fusi P.;
RT "Human sialidase NEU4 long and short are extrinsic proteins bound to outer
RT mitochondrial membrane and the endoplasmic reticulum, respectively.";
RL Glycobiology 20:148-157(2010).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION (ISOFORM 1).
RX PubMed=21521691; DOI=10.1074/jbc.m111.231191;
RA Shiozaki K., Yamaguchi K., Takahashi K., Moriya S., Miyagi T.;
RT "Regulation of sialyl Lewis antigen expression in colon cancer cells by
RT sialidase NEU4.";
RL J. Biol. Chem. 286:21052-21061(2011).
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. Efficiently hydrolyzes gangliosides including alpha-
CC (2->3)-sialylated GD1a and GM3 and alpha-(2->8)-sialylated GD3
CC (PubMed:15847605, PubMed:21521691, PubMed:15213228). Hydrolyzes poly-
CC alpha-(2->8)-sialylated neural cell adhesion molecule NCAM1 likely at
CC growth cones, suppressing neurite outgrowth in hippocampal neurons (By
CC similarity). May desialylate sialyl Lewis A and X antigens at the cell
CC surface, down-regulating these glycan epitopes recognized by SELE/E
CC selectin in the initiation of cell adhesion and extravasation
CC (PubMed:21521691). Has sialidase activity toward mucin, fetuin and
CC sialyllactose (PubMed:15847605). {ECO:0000250|UniProtKB:Q8BZL1,
CC ECO:0000269|PubMed:15213228, ECO:0000269|PubMed:15847605,
CC ECO:0000269|PubMed:21521691}.
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:14962670, ECO:0000269|PubMed:15213228,
CC ECO:0000269|PubMed:15847605, ECO:0000269|PubMed:21521691};
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:15847605};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48137;
CC Evidence={ECO:0000305|PubMed:15847605};
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:15847605, ECO:0000269|PubMed:21521691};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47901;
CC Evidence={ECO:0000305|PubMed:15847605, ECO:0000305|PubMed:21521691};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ganglioside GM2 + H2O = N-acetyl-beta-D-galactosaminyl-(1->4)-
CC beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1<->1')-ceramide + N-
CC acetylneuraminate; Xref=Rhea:RHEA:48172, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:35418, ChEBI:CHEBI:79218, ChEBI:CHEBI:90085;
CC Evidence={ECO:0000269|PubMed:15847605};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48173;
CC Evidence={ECO:0000305|PubMed:15847605};
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:0000269|PubMed:15847605};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48069;
CC Evidence={ECO:0000305|PubMed:15847605};
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:15847605};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47833;
CC Evidence={ECO:0000305|PubMed:15847605};
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:0000269|PubMed:15847605};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47857;
CC Evidence={ECO:0000305|PubMed:15847605};
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:15847605};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48121;
CC Evidence={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:0000269|PubMed:15847605};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48125;
CC Evidence={ECO:0000305|PubMed:15847605};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 3.2. {ECO:0000269|PubMed:14962670};
CC -!- INTERACTION:
CC Q8WWR8; Q99750: MDFI; NbExp=4; IntAct=EBI-746964, EBI-724076;
CC Q8WWR8; O15162: PLSCR1; NbExp=2; IntAct=EBI-746964, EBI-740019;
CC Q8WWR8-2; P63010: AP2B1; NbExp=3; IntAct=EBI-10277551, EBI-432924;
CC Q8WWR8-2; P63010-2: AP2B1; NbExp=3; IntAct=EBI-10277551, EBI-11529439;
CC Q8WWR8-2; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-10277551, EBI-3867333;
CC Q8WWR8-2; P59990: KRTAP12-1; NbExp=3; IntAct=EBI-10277551, EBI-10210845;
CC Q8WWR8-2; Q3LI76: KRTAP15-1; NbExp=3; IntAct=EBI-10277551, EBI-11992140;
CC Q8WWR8-2; Q3SYF9: KRTAP19-7; NbExp=3; IntAct=EBI-10277551, EBI-10241353;
CC Q8WWR8-2; Q3LI66: KRTAP6-2; NbExp=3; IntAct=EBI-10277551, EBI-11962084;
CC Q8WWR8-2; P15884: TCF4; NbExp=3; IntAct=EBI-10277551, EBI-533224;
CC Q8WWR8-2; Q15654: TRIP6; NbExp=3; IntAct=EBI-10277551, EBI-742327;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane
CC {ECO:0000269|PubMed:21521691}; Peripheral membrane protein. Endoplasmic
CC reticulum membrane {ECO:0000269|PubMed:15847605}; Peripheral membrane
CC protein. Microsome membrane {ECO:0000269|PubMed:15847605}; Peripheral
CC membrane protein. Mitochondrion membrane {ECO:0000269|PubMed:15847605,
CC ECO:0000269|PubMed:19797320}; Peripheral membrane protein. Cell
CC projection, neuron projection {ECO:0000250|UniProtKB:Q8BZL1}.
CC Note=Predominantly associates with endoplasmic reticulum membranes.
CC Only a small fraction associates with mitochondrial and plasma
CC membranes. {ECO:0000269|PubMed:19797320, ECO:0000269|PubMed:21521691}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:15847605}; Peripheral membrane protein.
CC Mitochondrion outer membrane {ECO:0000269|PubMed:15847605,
CC ECO:0000269|PubMed:19797320}; Peripheral membrane protein. Lysosome
CC lumen {ECO:0000269|PubMed:15213228}. Note=According to PubMed:15213228,
CC isoform 2 is soluble, N-glycosylated and found in the lumen of
CC lysosomes. However, no signal sequence nor N-glycosylation site is
CC predicted from the sequence.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8WWR8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8WWR8-2; Sequence=VSP_037491;
CC Name=3;
CC IsoId=Q8WWR8-3; Sequence=VSP_047123;
CC -!- TISSUE SPECIFICITY: [Isoform 1]: Predominant form in liver. Also
CC expressed in brain, kidney and colon. {ECO:0000269|PubMed:14962670,
CC ECO:0000269|PubMed:15847605}.
CC -!- TISSUE SPECIFICITY: [Isoform 2]: Highly expressed in brain and at lower
CC levels in kidney and liver. {ECO:0000269|PubMed:15847605}.
CC -!- INDUCTION: Down-regulated during monocyte to macrophage
CC differentiation. {ECO:0000269|PubMed:15885103}.
CC -!- PTM: [Isoform 2]: N-glycosylated. {ECO:0000269|PubMed:15213228}.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 33 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAP34475.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AJ277883; CAC81904.1; -; mRNA.
DR EMBL; AK289421; BAF82110.1; -; mRNA.
DR EMBL; AY203952; AAP34475.1; ALT_FRAME; mRNA.
DR EMBL; AC114730; AAX82022.1; -; Genomic_DNA.
DR EMBL; CH471063; EAW71296.1; -; Genomic_DNA.
DR EMBL; BC012899; AAH12899.2; -; mRNA.
DR CCDS; CCDS2553.1; -. [Q8WWR8-2]
DR CCDS; CCDS54441.1; -. [Q8WWR8-3]
DR CCDS; CCDS54442.1; -. [Q8WWR8-1]
DR RefSeq; NP_001161071.1; NM_001167599.2. [Q8WWR8-3]
DR RefSeq; NP_001161072.1; NM_001167600.2. [Q8WWR8-1]
DR RefSeq; NP_001161073.1; NM_001167601.2. [Q8WWR8-1]
DR RefSeq; NP_001161074.1; NM_001167602.2. [Q8WWR8-1]
DR RefSeq; NP_542779.2; NM_080741.3. [Q8WWR8-2]
DR AlphaFoldDB; Q8WWR8; -.
DR SMR; Q8WWR8; -.
DR BioGRID; 126209; 63.
DR IntAct; Q8WWR8; 23.
DR MINT; Q8WWR8; -.
DR STRING; 9606.ENSP00000320318; -.
DR BindingDB; Q8WWR8; -.
DR ChEMBL; CHEMBL4174; -.
DR SwissLipids; SLP:000001400; -. [Q8WWR8-2]
DR SwissLipids; SLP:000001401; -. [Q8WWR8-1]
DR CAZy; GH33; Glycoside Hydrolase Family 33.
DR GlyGen; Q8WWR8; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q8WWR8; -.
DR PhosphoSitePlus; Q8WWR8; -.
DR BioMuta; NEU4; -.
DR DMDM; 90110434; -.
DR MassIVE; Q8WWR8; -.
DR PaxDb; Q8WWR8; -.
DR PeptideAtlas; Q8WWR8; -.
DR PRIDE; Q8WWR8; -.
DR ProteomicsDB; 74925; -. [Q8WWR8-1]
DR ProteomicsDB; 74926; -. [Q8WWR8-2]
DR Antibodypedia; 34580; 172 antibodies from 25 providers.
DR DNASU; 129807; -.
DR Ensembl; ENST00000325935.10; ENSP00000320318.6; ENSG00000204099.12. [Q8WWR8-3]
DR Ensembl; ENST00000391969.6; ENSP00000375830.2; ENSG00000204099.12. [Q8WWR8-1]
DR Ensembl; ENST00000404257.5; ENSP00000385149.1; ENSG00000204099.12. [Q8WWR8-2]
DR Ensembl; ENST00000405370.5; ENSP00000384804.1; ENSG00000204099.12. [Q8WWR8-1]
DR Ensembl; ENST00000407683.6; ENSP00000385402.1; ENSG00000204099.12. [Q8WWR8-1]
DR Ensembl; ENST00000616490.3; ENSP00000482722.2; ENSG00000277926.4. [Q8WWR8-2]
DR Ensembl; ENST00000618866.4; ENSP00000483726.1; ENSG00000277926.4. [Q8WWR8-1]
DR Ensembl; ENST00000621851.4; ENSP00000478409.1; ENSG00000277926.4. [Q8WWR8-1]
DR Ensembl; ENST00000626600.2; ENSP00000485701.1; ENSG00000277926.4. [Q8WWR8-3]
DR Ensembl; ENST00000630923.2; ENSP00000486602.1; ENSG00000277926.4. [Q8WWR8-1]
DR GeneID; 129807; -.
DR KEGG; hsa:129807; -.
DR MANE-Select; ENST00000407683.6; ENSP00000385402.1; NM_001167600.3; NP_001161072.1.
DR UCSC; uc002wcm.4; human. [Q8WWR8-1]
DR CTD; 129807; -.
DR DisGeNET; 129807; -.
DR GeneCards; NEU4; -.
DR HGNC; HGNC:21328; NEU4.
DR HPA; ENSG00000204099; Tissue enriched (liver).
DR MIM; 608527; gene.
DR neXtProt; NX_Q8WWR8; -.
DR OpenTargets; ENSG00000204099; -.
DR PharmGKB; PA134917116; -.
DR VEuPathDB; HostDB:ENSG00000204099; -.
DR eggNOG; ENOG502QSFT; Eukaryota.
DR GeneTree; ENSGT00950000182944; -.
DR InParanoid; Q8WWR8; -.
DR OMA; GRTWHCG; -.
DR PhylomeDB; Q8WWR8; -.
DR TreeFam; TF331063; -.
DR BRENDA; 3.2.1.18; 2681.
DR PathwayCommons; Q8WWR8; -.
DR Reactome; R-HSA-1660662; Glycosphingolipid metabolism. [Q8WWR8-2]
DR Reactome; R-HSA-4085001; Sialic acid metabolism.
DR SABIO-RK; Q8WWR8; -.
DR SignaLink; Q8WWR8; -.
DR BioGRID-ORCS; 129807; 12 hits in 1069 CRISPR screens.
DR GeneWiki; NEU4; -.
DR GenomeRNAi; 129807; -.
DR Pharos; Q8WWR8; Tchem.
DR PRO; PR:Q8WWR8; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q8WWR8; protein.
DR Bgee; ENSG00000204099; Expressed in mucosa of transverse colon and 89 other tissues.
DR ExpressionAtlas; Q8WWR8; baseline and differential.
DR Genevisible; Q8WWR8; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0043202; C:lysosomal lumen; TAS:Reactome.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0005741; C:mitochondrial outer membrane; IDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IEA:UniProtKB-SubCell.
DR GO; GO:0019866; C:organelle inner membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
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:0006689; P:ganglioside catabolic process; IDA:UniProtKB.
DR GO; GO:0006516; P:glycoprotein catabolic process; IDA:UniProtKB.
DR GO; GO:0010977; P:negative regulation of neuron projection development; IEA:Ensembl.
DR GO; GO:0009313; P:oligosaccharide catabolic process; IDA:UniProtKB.
DR InterPro; IPR011040; Sialidase.
DR InterPro; IPR026946; Sialidase-4.
DR InterPro; IPR026856; Sialidase_fam.
DR InterPro; IPR036278; Sialidase_sf.
DR PANTHER; PTHR10628; PTHR10628; 1.
DR PANTHER; PTHR10628:SF22; PTHR10628:SF22; 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;
KW Cell projection; Endoplasmic reticulum; Glycosidase; Hydrolase;
KW Lipid degradation; Lipid metabolism; Lysosome; Membrane; Microsome;
KW Mitochondrion; Mitochondrion inner membrane; Mitochondrion outer membrane;
KW Reference proteome; Repeat.
FT CHAIN 1..484
FT /note="Sialidase-4"
FT /id="PRO_0000208906"
FT REPEAT 127..138
FT /note="BNR 1"
FT REPEAT 200..211
FT /note="BNR 2"
FT REPEAT 251..262
FT /note="BNR 3"
FT REGION 284..357
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 22..25
FT /note="FRIP motif"
FT ACT_SITE 47
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT ACT_SITE 48
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT ACT_SITE 419
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT ACT_SITE 440
FT /evidence="ECO:0000255"
FT BINDING 23
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 43
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 177
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 179
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 222
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 242
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 389
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1
FT /note="M -> MMSSAAFPRWLSM (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_037491"
FT VAR_SEQ 1
FT /note="M -> MMSSAAFPRWLQSM (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_047123"
FT VARIANT 301
FT /note="G -> R (in dbSNP:rs11545301)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:14962670, ECO:0000269|PubMed:15498874"
FT /id="VAR_067458"
FT MUTAGEN 5
FT /note="R->A: Impairs mitochondrial targeting."
FT /evidence="ECO:0000269|PubMed:15847605"
FT CONFLICT 184
FT /note="R -> L (in Ref. 1; CAC81904)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 484 AA; 51572 MW; 14A878C2A9F18863 CRC64;
MGVPRTPSRT VLFERERTGL TYRVPSLLPV PPGPTLLAFV EQRLSPDDSH AHRLVLRRGT
LAGGSVRWGA LHVLGTAALA EHRSMNPCPV HDAGTGTVFL FFIAVLGHTP EAVQIATGRN
AARLCCVASR DAGLSWGSAR DLTEEAIGGA VQDWATFAVG PGHGVQLPSG RLLVPAYTYR
VDRRECFGKI CRTSPHSFAF YSDDHGRTWR CGGLVPNLRS GECQLAAVDG GQAGSFLYCN
ARSPLGSRVQ ALSTDEGTSF LPAERVASLP ETAWGCQGSI VGFPAPAPNR PRDDSWSVGP
GSPLQPPLLG PGVHEPPEEA AVDPRGGQVP GGPFSRLQPR GDGPRQPGPR PGVSGDVGSW
TLALPMPFAA PPQSPTWLLY SHPVGRRARL HMGIRLSQSP LDPRSWTEPW VIYEGPSGYS
DLASIGPAPE GGLVFACLYE SGARTSYDEI SFCTFSLREV LENVPASPKP PNLGDKPRGC
CWPS
