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 27-MAR-2024, entry version 179. 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=a ganglioside GM3 + H2O = a 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=a ganglioside GM3 (d18:1(4E)) + H2O = a beta-D-Gal-(1->4)- CC beta-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=a ganglioside GM2 + H2O = a ganglioside GA2 + 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=a ganglioside GM2 (d18:1(4E)) + H2O = a 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=a ganglioside GD1a + H2O = a 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=a ganglioside GD1a (d18:1(4E)) + H2O = a 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=a ganglioside GD3 + H2O = a ganglioside GM3 + N- CC acetylneuraminate; Xref=Rhea:RHEA:48120, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:35418, 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=a ganglioside GD3 (d18:1(4E)) + H2O = a 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 64. DR IntAct; Q8WWR8; 24. 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; 9606-ENSP00000320318; -. DR PeptideAtlas; Q8WWR8; -. DR ProteomicsDB; 74925; -. [Q8WWR8-1] DR ProteomicsDB; 74926; -. [Q8WWR8-2] DR Antibodypedia; 34580; 180 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 AGR; HGNC:21328; -. 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 OrthoDB; 5482010at2759; -. DR PhylomeDB; Q8WWR8; -. DR TreeFam; TF331063; -. DR BRENDA; 3.2.1.18; 2681. DR PathwayCommons; Q8WWR8; -. DR Reactome; R-HSA-4085001; Sialic acid metabolism. DR Reactome; R-HSA-9840310; Glycosphingolipid catabolism. [Q8WWR8-2] DR SABIO-RK; Q8WWR8; -. DR SignaLink; Q8WWR8; -. DR BioGRID-ORCS; 129807; 12 hits in 1148 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 cell types or tissues. DR ExpressionAtlas; Q8WWR8; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB. 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 CDD; cd15482; Sialidase_non-viral; 1. DR Gene3D; 2.120.10.10; -; 2. DR InterPro; IPR011040; Sialidase. DR InterPro; IPR026856; Sialidase_fam. DR InterPro; IPR036278; Sialidase_sf. DR PANTHER; PTHR10628; SIALIDASE; 1. DR PANTHER; PTHR10628:SF22; SIALIDASE-4; 1. DR Pfam; PF13088; BNR_2; 1. DR SUPFAM; SSF50939; Sialidases; 1. DR Genevisible; Q8WWR8; HS. 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 //