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Q8WWR8 (NEUR4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 108. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Sialidase-4

EC=3.2.1.18
Alternative name(s):
N-acetyl-alpha-neuraminidase 4
Gene names
Name:NEU4
ORF Names:LP5125
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length484 AA.
Sequence statusComplete.
Protein existenceEvidence 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.7

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.7

Subcellular location

Isoform 1: Membrane; Peripheral membrane protein Ref.1 Ref.7.

Isoform 2: Lysosome lumen. Note: According to Ref.7, 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.7

Tissue specificity

Ubiquitous with higher expression in heart, skeletal muscle, liver and placenta. Ref.1

Induction

Down-regulated during monocyte to macrophage differentiation. Ref.8

Post-translational modification

According to Ref.7, 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.7). Ref.7

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
   Biological processCarbohydrate metabolism
Lipid degradation
Lipid metabolism
   Cellular componentLysosome
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainRepeat
   Molecular functionGlycosidase
Hydrolase
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processganglioside catabolic process

Inferred from direct assay Ref.7. Source: UniProtKB

glycoprotein catabolic process

Inferred from direct assay Ref.7. Source: UniProtKB

glycosphingolipid metabolic process

Traceable author statement. Source: Reactome

oligosaccharide catabolic process

Inferred from direct assay Ref.7. Source: UniProtKB

small molecule metabolic process

Traceable author statement. Source: Reactome

sphingolipid metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentlysosomal lumen

Traceable author statement. Source: Reactome

lysosome

Inferred from direct assay Ref.7. Source: UniProtKB

mitochondrion

Inferred from electronic annotation. Source: Ensembl

organelle inner membrane

Inferred from direct assay Ref.1. Source: UniProtKB

   Molecular_functionexo-alpha-(2->3)-sialidase activity

Inferred from electronic annotation. Source: UniProtKB-EC

exo-alpha-(2->6)-sialidase activity

Inferred from electronic annotation. Source: UniProtKB-EC

exo-alpha-(2->8)-sialidase activity

Inferred from electronic annotation. Source: UniProtKB-EC

exo-alpha-sialidase activity

Inferred from direct assay Ref.1Ref.7. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 16189514PubMed 19060904PubMed 19447967PubMed 21516116. Source: IntAct

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

MDFIQ997504EBI-746964,EBI-724076
PLSCR1O151622EBI-746964,EBI-740019

Alternative products

This entry describes 3 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
Isoform 3 (identifier: Q8WWR8-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MMSSAAFPRWLQSM
Note: Gene prediction based on EST data.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 484484Sialidase-4
PRO_0000208906

Regions

Repeat127 – 13812BNR 1
Repeat200 – 21112BNR 2
Repeat251 – 26212BNR 3
Motif22 – 254FRIP motif
Compositional bias284 – 37592Pro-rich

Sites

Active site471Proton acceptor By similarity
Active site481Proton acceptor By similarity
Active site4191Nucleophile By similarity
Active site4401 Potential
Binding site231Substrate By similarity
Binding site431Substrate By similarity
Binding site1771Substrate By similarity
Binding site1791Substrate By similarity
Binding site2221Substrate By similarity
Binding site2421Substrate By similarity
Binding site3891Substrate By similarity

Natural variations

Alternative sequence11M → MMSSAAFPRWLSM in isoform 2.
VSP_037491
Alternative sequence11M → MMSSAAFPRWLQSM in isoform 3.
VSP_047123
Natural variant3011G → R. Ref.1 Ref.2 Ref.3
Corresponds to variant rs11545301 [ dbSNP | Ensembl ].
VAR_067458

Experimental info

Sequence conflict1841R → L in CAC81904. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified March 7, 2006. Version 3.
Checksum: 14A878C2A9F18863

FASTA48451,572
        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 

« Hide

Isoform 2 [UniParc].

Checksum: 1DE1395862011A36
Show »

FASTA49652,938
Isoform 3 [UniParc].

Checksum: C933EFAEC7383F69
Show »

FASTA49753,066

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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.
[7]"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.
[8]"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.
CH471063 Genomic DNA. Translation: EAW71296.1.
BC012899 mRNA. Translation: AAH12899.2.
CCDSCCDS2553.1. [Q8WWR8-2]
CCDS54441.1. [Q8WWR8-3]
CCDS54442.1. [Q8WWR8-1]
RefSeqNP_001161071.1. NM_001167599.2. [Q8WWR8-3]
NP_001161072.1. NM_001167600.2. [Q8WWR8-1]
NP_001161073.1. NM_001167601.2. [Q8WWR8-1]
NP_001161074.1. NM_001167602.2. [Q8WWR8-1]
NP_542779.2. NM_080741.3. [Q8WWR8-2]
UniGeneHs.551747.

3D structure databases

ProteinModelPortalQ8WWR8.
SMRQ8WWR8. Positions 22-344, 371-461.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid126209. 5 interactions.
IntActQ8WWR8. 5 interactions.
MINTMINT-1447950.
STRING9606.ENSP00000385149.

Chemistry

BindingDBQ8WWR8.
ChEMBLCHEMBL4174.

Protein family/group databases

CAZyGH33. Glycoside Hydrolase Family 33.

PTM databases

PhosphoSiteQ8WWR8.

Polymorphism databases

DMDM90110434.

Proteomic databases

PaxDbQ8WWR8.
PRIDEQ8WWR8.

Protocols and materials databases

DNASU129807.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000325935; ENSP00000320318; ENSG00000204099. [Q8WWR8-3]
ENST00000391969; ENSP00000375830; ENSG00000204099. [Q8WWR8-1]
ENST00000404257; ENSP00000385149; ENSG00000204099. [Q8WWR8-2]
ENST00000405370; ENSP00000384804; ENSG00000204099. [Q8WWR8-1]
ENST00000407683; ENSP00000385402; ENSG00000204099. [Q8WWR8-1]
GeneID129807.
KEGGhsa:129807.
UCSCuc002wcm.3. human. [Q8WWR8-1]
uc002wcn.2. human. [Q8WWR8-2]

Organism-specific databases

CTD129807.
GeneCardsGC02P242770.
HGNCHGNC:21328. NEU4.
HPAHPA037394.
HPA037395.
MIM608527. gene.
neXtProtNX_Q8WWR8.
PharmGKBPA134917116.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG84455.
HOGENOMHOG000233778.
HOVERGENHBG052608.
InParanoidQ8WWR8.
KOK12357.
OMAMNPCPVL.
OrthoDBEOG7MSMNP.
PhylomeDBQ8WWR8.
TreeFamTF331063.

Enzyme and pathway databases

BRENDA3.2.1.18. 2681.
ReactomeREACT_111217. Metabolism.
REACT_17015. Metabolism of proteins.
SABIO-RKQ8WWR8.

Gene expression databases

ArrayExpressQ8WWR8.
BgeeQ8WWR8.
CleanExHS_NEU4.
GenevestigatorQ8WWR8.

Family and domain databases

Gene3D2.120.10.10. 2 hits.
InterProIPR026946. Sialidase-4.
IPR026856. Sialidase_fam.
IPR011040. Sialidases.
[Graphical view]
PANTHERPTHR10628. PTHR10628. 1 hit.
PTHR10628:SF8. PTHR10628:SF8. 1 hit.
SUPFAMSSF50939. SSF50939. 2 hits.
ProtoNetSearch...

Other

GeneWikiNEU4.
GenomeRNAi129807.
NextBio35534929.
PROQ8WWR8.
SOURCESearch...

Entry information

Entry nameNEUR4_HUMAN
AccessionPrimary (citable) accession number: Q8WWR8
Secondary accession number(s): A8K056, J3KNJ5, Q96D64
Entry history
Integrated into UniProtKB/Swiss-Prot: June 7, 2004
Last sequence update: March 7, 2006
Last modified: July 9, 2014
This is version 108 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM

Glycosyl hydrolases

Classification of glycosyl hydrolase families and list of entries