Q8WWR8 (NEUR4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sialidase-4
EC=3.2.1.18

Alternative name(s):
N-acetyl-alpha-neuraminidase 4

Gene names

Name:	NEU4
ORF Names:	LP5125

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	484 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May function in lysosomal catabolism of sialylated glycoconjugates. Has sialidase activity towards synthetic substrates, such as 2'-(4-methylumbelliferyl)-alpha-D-N-acetylneuraminic acid (4-MU-NANA or 4MU-NeuAc). Has a broad substrate specificity being active on glycoproteins, oligosaccharides and sialylated glycolipids. Ref.1 Ref.6
Catalytic activity	Hydrolysis of alpha-(2->3)-, alpha-(2->6)-, alpha-(2->8)- glycosidic linkages of terminal sialic acid residues in oligosaccharides, glycoproteins, glycolipids, colominic acid and synthetic substrates. Ref.6
Subcellular location	Isoform 1: Membrane; Peripheral membrane protein Ref.1 Ref.6. Isoform 2: Lysosome lumen. Note: According to Ref.6, isoform 2 is soluble, N-glycosylated and found in the lumen of lysosomes. However, no signal sequence nor N-glycosylation site is predicted from the sequence. Ref.1 Ref.6
Tissue specificity	Ubiquitous with higher expression in heart, skeletal muscle, liver and placenta. Ref.1
Induction	Down-regulated during monocyte to macrophage differentiation. Ref.7
Post-translational modification	According to Ref.6, phosphorylation of mannose residues may ensure efficient transport of isoform 2 to the lysosomes via the mannose 6-phosphate receptor. Isoform 2 is glycosylated (Ref.6). Ref.6
Sequence similarities	Belongs to the glycosyl hydrolase 33 family. Contains 3 BNR repeats.
Biophysicochemical properties	pH dependence: Optimum pH is 3.2.
Sequence caution	The sequence AAP34475.1 differs from that shown. Reason: Frameshift at position 291.

Ontologies

Keywords
Cellular component	Lysosome Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat
Molecular function	Glycosidase Hydrolase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	glycosphingolipid metabolic process Traceable author statement. Source: Reactome phospholipid metabolic process Traceable author statement. Source: Reactome small molecule metabolic process Traceable author statement. Source: Reactome
Cellular_component	lysosomal lumen Traceable author statement. Source: Reactome organelle inner membrane Inferred from direct assay Ref.1. Source: UniProtKB
Molecular_function	exo-alpha-(2->3)-sialidase activity Inferred from electronic annotation. Source: EC exo-alpha-(2->6)-sialidase activity Inferred from electronic annotation. Source: EC exo-alpha-(2->8)-sialidase activity Inferred from electronic annotation. Source: EC exo-alpha-sialidase activity Inferred from direct assay Ref.1. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MDFI	Q99750	3	EBI-746964,EBI-724076
PLSCR1	O15162	2	EBI-746964,EBI-740019

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8WWR8-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q8WWR8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MMSSAAFPRWLSM

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 484	484	Sialidase-4		PRO_0000208906
Regions
	Repeat	127 – 138	12	BNR 1
	Repeat	200 – 211	12	BNR 2
	Repeat	251 – 262	12	BNR 3
	Motif	22 – 25	4	FRIP motif
	Compositional bias	284 – 375	92	Pro-rich
Sites
	Active site	48	1	Proton acceptor By similarity
	Active site	419	1	Nucleophile By similarity
	Active site	440	1	Potential
	Binding site	23	1	Substrate By similarity
	Binding site	389	1	Substrate By similarity
Natural variations
	Alternative sequence	1	1	M → MMSSAAFPRWLSM in isoform 2.		VSP_037491
	Natural variant	301	1	G → R. Ref.1 Ref.2 Ref.3 Corresponds to variant rs11545301 [ dbSNP | Ensembl ].		VAR_067458
Experimental info
	Sequence conflict	184	1	R → L in CAC81904. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 7, 2006. Version 3. Checksum: 14A878C2A9F18863	FASTA	484	51,572
	10 20 30 40 50 60 MGVPRTPSRT VLFERERTGL TYRVPSLLPV PPGPTLLAFV EQRLSPDDSH AHRLVLRRGT 70 80 90 100 110 120 LAGGSVRWGA LHVLGTAALA EHRSMNPCPV HDAGTGTVFL FFIAVLGHTP EAVQIATGRN 130 140 150 160 170 180 AARLCCVASR DAGLSWGSAR DLTEEAIGGA VQDWATFAVG PGHGVQLPSG RLLVPAYTYR 190 200 210 220 230 240 VDRRECFGKI CRTSPHSFAF YSDDHGRTWR CGGLVPNLRS GECQLAAVDG GQAGSFLYCN 250 260 270 280 290 300 ARSPLGSRVQ ALSTDEGTSF LPAERVASLP ETAWGCQGSI VGFPAPAPNR PRDDSWSVGP 310 320 330 340 350 360 GSPLQPPLLG PGVHEPPEEA AVDPRGGQVP GGPFSRLQPR GDGPRQPGPR PGVSGDVGSW 370 380 390 400 410 420 TLALPMPFAA PPQSPTWLLY SHPVGRRARL HMGIRLSQSP LDPRSWTEPW VIYEGPSGYS 430 440 450 460 470 480 DLASIGPAPE GGLVFACLYE SGARTSYDEI SFCTFSLREV LENVPASPKP PNLGDKPRGC CWPS
	Isoform 2 [UniParc]. Checksum: 1DE1395862011A36	FASTA	496	52,938
	10 20 30 40 50 60 MMSSAAFPRW LSMGVPRTPS RTVLFERERT GLTYRVPSLL PVPPGPTLLA FVEQRLSPDD 70 80 90 100 110 120 SHAHRLVLRR GTLAGGSVRW GALHVLGTAA LAEHRSMNPC PVHDAGTGTV FLFFIAVLGH 130 140 150 160 170 180 TPEAVQIATG RNAARLCCVA SRDAGLSWGS ARDLTEEAIG GAVQDWATFA VGPGHGVQLP 190 200 210 220 230 240 SGRLLVPAYT YRVDRRECFG KICRTSPHSF AFYSDDHGRT WRCGGLVPNL RSGECQLAAV 250 260 270 280 290 300 DGGQAGSFLY CNARSPLGSR VQALSTDEGT SFLPAERVAS LPETAWGCQG SIVGFPAPAP 310 320 330 340 350 360 NRPRDDSWSV GPGSPLQPPL LGPGVHEPPE EAAVDPRGGQ VPGGPFSRLQ PRGDGPRQPG 370 380 390 400 410 420 PRPGVSGDVG SWTLALPMPF AAPPQSPTWL LYSHPVGRRA RLHMGIRLSQ SPLDPRSWTE 430 440 450 460 470 480 PWVIYEGPSG YSDLASIGPA PEGGLVFACL YESGARTSYD EISFCTFSLR EVLENVPASP 490 KPPNLGDKPR GCCWPS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and characterization of NEU4, the fourth member of the human sialidase gene family." Monti E., Bassi M.T., Bresciani R., Civini S., Croci G.L., Papini N., Riboni M., Zanchetti G., Ballabio A., Preti A., Tettamanti G., Venerando B., Borsani G. Genomics 83:445-453(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, VARIANT ARG-301. Tissue: Fibroblast.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ARG-301. Tissue: Mammary gland.
[3]	"Large-scale cDNA transfection screening for genes related to cancer development and progression." Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X., Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X. , Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J. Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ARG-301.
[4]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Oligodendroglioma.
[6]	"Neu4, a novel human lysosomal lumen sialidase, confers normal phenotype to sialidosis and galactosialidosis cells." Seyrantepe V., Landry K., Trudel S., Hassan J.A., Morales C.R., Pshezhetsky A.V. J. Biol. Chem. 279:37021-37029(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, ALTERNATIVE SPLICING (ISOFORM 2), CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, GLYCOSYLATION.
[7]	"Differential expression of endogenous sialidases of human monocytes during cellular differentiation into macrophages." Stamatos N.M., Liang F., Nan X., Landry K., Cross A.S., Wang L.X., Pshezhetsky A.V. FEBS J. 272:2545-2556(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ277883 mRNA. Translation: CAC81904.1. AK289421 mRNA. Translation: BAF82110.1. AY203952 mRNA. Translation: AAP34475.1. Frameshift. AC114730 Genomic DNA. Translation: AAX82022.1. BC012899 mRNA. Translation: AAH12899.2.
IPI	IPI00790962. IPI00954297.
RefSeq	NP_001161071.1. NM_001167599.1. NP_001161072.1. NM_001167600.1. NP_001161073.1. NM_001167601.1. NP_001161074.1. NM_001167602.1. NP_542779.2. NM_080741.2.
UniGene	Hs.551747.
3D structure databases
ProteinModelPortal	Q8WWR8.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8WWR8. 4 interactions.
MINT	MINT-1447950.
STRING	9606.ENSP00000385149.
Protein family/group databases
CAZy	GH33. Glycoside Hydrolase Family 33.
PTM databases
PhosphoSite	Q8WWR8.
Polymorphism databases
DMDM	90110434.
Proteomic databases
PaxDb	Q8WWR8.
PRIDE	Q8WWR8.
Protocols and materials databases
DNASU	129807.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000391969; ENSP00000375830; ENSG00000204099. ENST00000404257; ENSP00000385149; ENSG00000204099. ENST00000405370; ENSP00000384804; ENSG00000204099. ENST00000407683; ENSP00000385402; ENSG00000204099.
GeneID	129807.
KEGG	hsa:129807.
UCSC	uc002wcm.3. human. uc002wcn.2. human.
Organism-specific databases
CTD	129807.
GeneCards	GC02P242770.
HGNC	HGNC:21328. NEU4.
HPA	HPA037395.
MIM	608527. gene.
neXtProt	NX_Q8WWR8.
PharmGKB	PA134917116.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG84455.
HOGENOM	HOG000233778.
HOVERGEN	HBG052608.
InParanoid	Q8WWR8.
KO	K12357.
OrthoDB	EOG43BMNR.
Enzyme and pathway databases
BRENDA	3.2.1.18. 2681.
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	Q8WWR8.
Bgee	Q8WWR8.
CleanEx	HS_NEU4.
Genevestigator	Q8WWR8.
GermOnline	ENSG00000204099. Homo sapiens.
Family and domain databases
Gene3D	2.120.10.10. 2 hits.
InterPro	IPR026946. Sialidase-4. IPR026856. Sialidase_fam. IPR011040. Sialidases. [Graphical view]
PANTHER	PTHR10628. PTHR10628. 1 hit. PTHR10628:SF8. PTHR10628:SF8. 1 hit.
SUPFAM	SSF50939. Sialidase. 1 hit.
ProtoNet	Search...
Other
BindingDB	Q8WWR8.
ChEMBL	CHEMBL4174.
GenomeRNAi	129807.
NextBio	82644.
SOURCE	Search...

Entry information

Entry name

NEUR4_HUMAN

Accession

Primary (citable) accession number: Q8WWR8
Secondary accession number(s): A8K056, Q96D64

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 7, 2004
Last sequence update:	March 7, 2006
Last modified:	May 1, 2013
This is version 94 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.