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Q9Y3R4 (NEUR2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 115. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Sialidase-2

EC=3.2.1.18
Alternative name(s):
Cytosolic sialidase
N-acetyl-alpha-neuraminidase 2
Gene names
Name:NEU2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length380 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalyzes the removal of sialic acid (N-acetylneuraminic acid) moities from glycoproteins, oligosaccharides and gangliosides. Ref.5 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.5 Ref.6

Subcellular location

Cytoplasm By similarity.

Tissue specificity

Expressed in skeletal muscle, fetal liver and embryonic carcinoma cell line NT2-D1. Ref.1

Sequence similarities

Belongs to the glycosyl hydrolase 33 family.

Contains 2 BNR repeats.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 380380Sialidase-2
PRO_0000208899

Regions

Repeat127 – 13812BNR 1
Repeat197 – 20812BNR 2
Motif20 – 234FRIP motif

Sites

Active site461Proton acceptor Ref.6 Ref.8
Active site3341Nucleophile Ref.6 Ref.8
Active site3551 Potential
Binding site211Substrate
Binding site411Substrate
Binding site1791Substrate
Binding site1811Substrate
Binding site2181Substrate
Binding site2371Substrate
Binding site3041Substrate

Natural variations

Natural variant111S → R.
Corresponds to variant rs2233384 [ dbSNP | Ensembl ].
VAR_024461
Natural variant411R → Q Reduced activity; increased sensitivity to inhibition by oseltamivir carboxylate. Ref.9
Corresponds to variant rs2233385 [ dbSNP | Ensembl ].
VAR_024462
Natural variant1451A → T.
Corresponds to variant rs2233390 [ dbSNP | Ensembl ].
VAR_049204
Natural variant1681H → N. Ref.1 Ref.4
Corresponds to variant rs2233391 [ dbSNP | Ensembl ].
VAR_055311
Natural variant1821R → Q.
Corresponds to variant rs2233393 [ dbSNP | Ensembl ].
VAR_055312

Experimental info

Mutagenesis461D → A: Loss of enzyme activity. Ref.6
Mutagenesis2181E → A or Q: Loss of enzyme activity. Ref.6
Mutagenesis2701Q → E: No effect on enzyme activity. Ref.6

Secondary structure

............................................................... 380
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9Y3R4 [UniParc].

Last modified May 5, 2009. Version 2.
Checksum: AD7B08C478F4D0D9

FASTA38042,254
        10         20         30         40         50         60 
MASLPVLQKE SVFQSGAHAY RIPALLYLPG QQSLLAFAEQ RASKKDEHAE LIVLRRGDYD 

        70         80         90        100        110        120 
APTHQVQWQA QEVVAQARLD GHRSMNPCPL YDAQTGTLFL FFIAIPGQVT EQQQLQTRAN 

       130        140        150        160        170        180 
VTRLCQVTST DHGRTWSSPR DLTDAAIGPA YREWSTFAVG PGHCLQLHDR ARSLVVPAYA 

       190        200        210        220        230        240 
YRKLHPIQRP IPSAFCFLSH DHGRTWARGH FVAQDTLECQ VAEVETGEQR VVTLNARSHL 

       250        260        270        280        290        300 
RARVQAQSTN DGLDFQESQL VKKLVEPPPQ GCQGSVISFP SPRSGPGSPA QWLLYTHPTH 

       310        320        330        340        350        360 
SWQRADLGAY LNPRPPAPEA WSEPVLLAKG SCAYSDLQSM GTGPDGSPLF GCLYEANDYE 

       370        380 
EIVFLMFTLK QAFPAEYLPQ 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and characterization of NEU2, a human gene homologous to rodent soluble sialidases."
Monti E., Preti A., Rossi E., Ballabio A., Borsani G.
Genomics 57:137-143(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY, VARIANT ASN-168.
[2]"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].
[3]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].
[4]"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], VARIANT ASN-168.
[5]"Properties of recombinant human cytosolic sialidase HsNEU2. The enzyme hydrolyzes monomerically dispersed GM1 ganglioside molecules."
Tringali C., Papini N., Fusi P., Croci G., Borsani G., Preti A., Tortora P., Tettamanti G., Venerando B., Monti E.
J. Biol. Chem. 279:3169-3179(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, FUNCTION.
[6]"Molecular insight into substrate recognition by human cytosolic sialidase NEU2."
Mozzi A., Mazzacuva P., Zampella G., Forcella M.E., Fusi P.A., Monti E.
Proteins 80:1123-1132(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, FUNCTION, ACTIVE SITE, MUTAGENESIS OF ASP-46; GLU-218 AND GLN-270.
[7]"Crystal structure of the human cytosolic sialidase Neu2. Evidence for the dynamic nature of substrate recognition."
Chavas L.M.G., Tringali C., Fusi P., Venerando B., Tettamanti G., Kato R., Monti E., Wakatsuki S.
J. Biol. Chem. 280:469-475(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.49 ANGSTROMS) IN COMPLEX WITH THE INHIBITOR 2-DEOXY-2,3-DEHYDRO-N-ACETYLNEURAMINIC ACID.
[8]"Tuning mechanism-based inactivators of neuraminidases: mechanistic and structural insights."
Buchini S., Gallat F.X., Greig I.R., Kim J.H., Wakatsuki S., Withers S.G.
Submitted (NOV-2013) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (2.52 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOG, ACTIVE SITE.
[9]"A nonsynonymous SNP in human cytosolic sialidase in a small Asian population results in reduced enzyme activity: potential link with severe adverse reactions to oseltamivir."
Li C.-Y., Yu Q., Ye Z.-Q., Sun Y., He Q., Li X.-M., Zhang W., Luo J., Gu X., Zheng X., Wei L.
Cell Res. 17:357-362(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT GLN-41.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Y16535 Genomic DNA. Translation: CAB41449.1.
AC106876 Genomic DNA. Translation: AAY24360.1.
CH471063 Genomic DNA. Translation: EAW71028.1.
BC069151 mRNA. Translation: AAH69151.1.
BC107053 mRNA. Translation: AAI07054.1.
RefSeqNP_005374.2. NM_005383.2.
UniGeneHs.532681.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1SNTX-ray1.75A1-380[»]
1SO7X-ray1.49A1-380[»]
1VCUX-ray2.85A/B1-380[»]
2F0ZX-ray2.80A1-380[»]
2F10X-ray2.90A1-380[»]
2F11X-ray2.57A1-380[»]
2F12X-ray2.27A1-380[»]
2F13X-ray2.26A1-380[»]
2F24X-ray1.76A1-380[»]
2F25X-ray1.95A/B1-380[»]
2F26X-ray1.58A1-380[»]
2F27X-ray2.15A/B1-380[»]
2F28X-ray1.67A1-380[»]
2F29X-ray2.92A/B1-380[»]
4NC5X-ray2.51A1-380[»]
4NCSX-ray2.20A1-380[»]
DisProtDP00261.
ProteinModelPortalQ9Y3R4.
SMRQ9Y3R4. Positions 1-377.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000233840.

Chemistry

BindingDBQ9Y3R4.
ChEMBLCHEMBL3200.

Protein family/group databases

CAZyGH33. Glycoside Hydrolase Family 33.

PTM databases

PhosphoSiteQ9Y3R4.

Polymorphism databases

DMDM229462907.

Proteomic databases

PaxDbQ9Y3R4.
PRIDEQ9Y3R4.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000233840; ENSP00000233840; ENSG00000115488.
GeneID4759.
KEGGhsa:4759.
UCSCuc010zmn.2. human.

Organism-specific databases

CTD4759.
GeneCardsGC02P233897.
H-InvDBHIX0029978.
HGNCHGNC:7759. NEU2.
HPACAB022336.
HPA034704.
MIM605528. gene.
neXtProtNX_Q9Y3R4.
PharmGKBPA31561.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG84455.
HOGENOMHOG000233778.
HOVERGENHBG052608.
InParanoidQ9Y3R4.
KOK12357.
OMAQSMGTGP.
OrthoDBEOG7MSMNP.
PhylomeDBQ9Y3R4.
TreeFamTF331063.

Enzyme and pathway databases

BRENDA3.2.1.18. 2681.
ReactomeREACT_111217. Metabolism.
SABIO-RKQ9Y3R4.

Gene expression databases

BgeeQ9Y3R4.
CleanExHS_NEU2.
GenevestigatorQ9Y3R4.

Family and domain databases

Gene3D2.120.10.10. 1 hit.
InterProIPR026945. Sialidase-2.
IPR026856. Sialidase_fam.
IPR011040. Sialidases.
[Graphical view]
PANTHERPTHR10628. PTHR10628. 1 hit.
PTHR10628:SF6. PTHR10628:SF6. 1 hit.
SUPFAMSSF50939. SSF50939. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceQ9Y3R4.
GeneWikiNEU2.
GenomeRNAi4759.
NextBio18332.
PROQ9Y3R4.
SOURCESearch...

Entry information

Entry nameNEUR2_HUMAN
AccessionPrimary (citable) accession number: Q9Y3R4
Secondary accession number(s): Q3KNW4, Q6NTB4
Entry history
Integrated into UniProtKB/Swiss-Prot: November 16, 2001
Last sequence update: May 5, 2009
Last modified: April 16, 2014
This is version 115 of the entry and version 2 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

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