UniProtKB - Q9Y3R4 (NEUR2_HUMAN)
Protein
Sialidase-2
Gene
NEU2
Organism
Homo sapiens (Human)
Status
Functioni
Exo-alpha-sialidase that catalyzes the hydrolytic cleavage of the terminal sialic acid (N-acetylneuraminic acid, Neu5Ac) of a glycan moiety in the catabolism of glycolipids, glycoproteins and oligosacharides (PubMed:14613940, PubMed:22228546). Recognizes sialyl linkage positions of the glycan moiety as well as the supramolecular organization of the sialoglycoconjugate. Displays preference for alpha-(2->3)-sialylated GD1a and GT1B gangliosides over alpha-(2->8)-sialylated GD1b, in both monomeric forms and micelles. Hydrolyzes monomeric GM1 ganglioside, but has no activity toward the miscellar form (PubMed:14613940). Has lower sialidase activity for glycoproteins such as fetuin and TF/transferrin that carry a mixture of alpha-(2->3) and alpha-(2->6)-sialyl linkages. Cleaves milk oligosaccharide alpha-(2->3)-sialyllactose, but is inactive toward alpha-(2->6)-sialyllactose isomer. Has no activity toward colominic acid, a homopolymer of alpha-(2->8)-linked Neu5Ac residues (PubMed:14613940).2 Publications
Catalytic activityi
- This reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forwardBy similarity direction.
- ganglioside GM3 + H2O = β-D-galactosyl-(1→4)-β-D-glucosyl-(1↔1)-ceramide + N-acetylneuraminate2 PublicationsThis reaction proceeds in the forward2 Publications direction.
- ganglioside GM2 + H2O = N-acetyl-β-D-galactosaminyl-(1→4)-β-D-galactosyl-(1→4)-β-D-glucosyl-(1↔1ʼ)-ceramide + N-acetylneuraminateBy similarityThis reaction proceeds in the forwardBy similarity direction.
- a neolactoside IV3-α-NeuAc-nLc4Cer(d18:1(4E)) + H2O = a neolactoside nLc4Cer(d18:1(4E)) + N-acetylneuraminate1 PublicationThis reaction proceeds in the forward1 Publication direction.
- H2O + N-acetyl-α-neuraminosyl-(2→3)-β-D-galactosyl-(1→4)-D-glucose = lactose + N-acetylneuraminate2 PublicationsThis reaction proceeds in the forward2 Publications direction.
- 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.2 Publications EC:3.2.1.18
Kineticsi
- KM=0.24 mM for ganglioside GM3 (in the presence of Triton X-100)1 Publication
- KM=0.14 mM for ganglioside GD1a (in the presence of Triton X-100)1 Publication
- KM=0.51 mM for ganglioside GD1b (in the presence of Triton X-100)1 Publication
- KM=0.38 mM for ganglioside GT1b (in the presence of Triton X-100)1 Publication
- KM=0.28 mM for neolactoside IV3-alpha-NeuAc-nLc4Cer(d18:1(4E)) (in the presence of Triton X-100)1 Publication
- KM=0.31 mM for alpha(2->3)-sialyllactose1 Publication
- Vmax=67 µmol/min/mg enzyme toward ganglioside GM3 (in the presence of Triton X-100)1 Publication
- Vmax=322 µmol/min/mg enzyme toward ganglioside GD1a (in the presence of Triton X-100)1 Publication
- Vmax=5.45 µmol/min/mg enzyme toward ganglioside GD1b (in the presence of Triton X-100)1 Publication
- Vmax=190 µmol/min/mg enzyme toward ganglioside GT1b (in the presence of Triton X-100)1 Publication
- Vmax=253 µmol/min/mg enzyme toward ganglioside neolactoside IV3-alpha-NeuAc-nLc4Cer(d18:1(4E)) (in the presence of Triton X-100)1 Publication
- Vmax=10 µmol/min/mg enzyme toward alpha(2->3)-sialyllactose1 Publication
- Vmax=12.7 µmol/min/mg enzyme toward fetuin1 Publication
- Vmax=0.75 µmol/min/mg enzyme toward TF/transferrin1 Publication
- Vmax=0.70 µmol/min/mg enzyme toward alpha-1-acid glycoprotein1 Publication
pH dependencei
Optimum pH is 5.6.1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 21 | Substrate | 1 | |
Binding sitei | 41 | Substrate | 1 | |
Active sitei | 46 | Proton acceptor1 Publication | 1 | |
Binding sitei | 179 | Substrate | 1 | |
Binding sitei | 181 | Substrate | 1 | |
Binding sitei | 218 | Substrate | 1 | |
Binding sitei | 237 | Substrate | 1 | |
Binding sitei | 304 | Substrate | 1 | |
Active sitei | 334 | Nucleophile | 1 | |
Active sitei | 355 | Sequence analysis | 1 |
GO - Molecular functioni
- exo-alpha-(2->3)-sialidase activity Source: UniProtKB
- exo-alpha-(2->6)-sialidase activity Source: UniProtKB-EC
- exo-alpha-(2->8)-sialidase activity Source: UniProtKB
- exo-alpha-sialidase activity Source: CAFA
GO - Biological processi
- cellular oligosaccharide catabolic process Source: CAFA
- ganglioside catabolic process Source: UniProtKB
- glycoprotein catabolic process Source: UniProtKB
- glycosphingolipid metabolic process Source: Reactome
- oligosaccharide catabolic process Source: UniProtKB
Keywordsi
Molecular function | Glycosidase, Hydrolase |
Biological process | Carbohydrate metabolism, Lipid degradation, Lipid metabolism |
Enzyme and pathway databases
BRENDAi | 3.2.1.18, 2681 |
PathwayCommonsi | Q9Y3R4 |
Reactomei | R-HSA-1660662, Glycosphingolipid metabolism R-HSA-4085001, Sialic acid metabolism |
SABIO-RKi | Q9Y3R4 |
Protein family/group databases
CAZyi | GH33, Glycoside Hydrolase Family 33 |
Chemistry databases
SwissLipidsi | SLP:000001360 |
Names & Taxonomyi
Protein namesi | Recommended name: Sialidase-2 (EC:3.2.1.182 Publications)Alternative name(s): Cytosolic sialidase N-acetyl-alpha-neuraminidase 2 |
Gene namesi | Name:NEU2 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:7759, NEU2 |
MIMi | 605528, gene |
neXtProti | NX_Q9Y3R4 |
VEuPathDBi | HostDB:ENSG00000115488.3 |
Subcellular locationi
Cytosol
- cytosol 1 Publication
Cytosol
- cytosol Source: UniProtKB
Other locations
- catalytic complex Source: CAFA
- cytoplasm Source: GO_Central
- intracellular membrane-bounded organelle Source: GO_Central
- membrane Source: GO_Central
Keywords - Cellular componenti
CytoplasmPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 46 | D → A: Loss of enzyme activity. 1 Publication | 1 | |
Mutagenesisi | 218 | E → A or Q: Loss of enzyme activity. 1 Publication | 1 | |
Mutagenesisi | 270 | Q → E: No effect on enzyme activity. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 4759 |
OpenTargetsi | ENSG00000115488 |
PharmGKBi | PA31561 |
Miscellaneous databases
Pharosi | Q9Y3R4, Tbio |
Chemistry databases
ChEMBLi | CHEMBL3200 |
DrugBanki | DB03991, 2-deoxy-2,3-dehydro-N-acetylneuraminic acid DB07960, 5-ACETAMIDO-5,6-DIHYDRO-4-HYDROXY-6-ISOBUTOXY-4H-PYRAN-2-CARBOXYLIC ACID DB00198, Oseltamivir DB00558, Zanamivir |
DrugCentrali | Q9Y3R4 |
Genetic variation databases
BioMutai | NEU2 |
DMDMi | 229462907 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000208899 | 1 – 380 | Sialidase-2Add BLAST | 380 |
Proteomic databases
MassIVEi | Q9Y3R4 |
PaxDbi | Q9Y3R4 |
PeptideAtlasi | Q9Y3R4 |
PRIDEi | Q9Y3R4 |
ProteomicsDBi | 86068 |
PTM databases
iPTMneti | Q9Y3R4 |
PhosphoSitePlusi | Q9Y3R4 |
Expressioni
Tissue specificityi
Expressed in skeletal muscle, fetal liver and embryonic carcinoma cell line NT2-D1.1 Publication
Gene expression databases
Bgeei | ENSG00000115488, Expressed in skin of leg and 13 other tissues |
Genevisiblei | Q9Y3R4, HS |
Organism-specific databases
HPAi | ENSG00000115488, Tissue enriched (skin) |
Interactioni
Binary interactionsi
Hide detailsQ9Y3R4
With | #Exp. | IntAct |
---|---|---|
CYSRT1 [A8MQ03] | 3 | EBI-10327976,EBI-3867333 |
NOTCH2NLA [Q7Z3S9] | 6 | EBI-10327976,EBI-945833 |
Protein-protein interaction databases
BioGRIDi | 110832, 24 interactors |
IntActi | Q9Y3R4, 21 interactors |
STRINGi | 9606.ENSP00000233840 |
Chemistry databases
BindingDBi | Q9Y3R4 |
Miscellaneous databases
RNActi | Q9Y3R4, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q9Y3R4 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q9Y3R4 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Repeati | 127 – 138 | BNR 1Add BLAST | 12 | |
Repeati | 197 – 208 | BNR 2Add BLAST | 12 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 20 – 23 | FRIP motif | 4 |
Sequence similaritiesi
Belongs to the glycosyl hydrolase 33 family.Curated
Keywords - Domaini
RepeatPhylogenomic databases
eggNOGi | ENOG502QSFT, Eukaryota |
GeneTreei | ENSGT00950000182944 |
HOGENOMi | CLU_024620_2_1_1 |
InParanoidi | Q9Y3R4 |
OMAi | HDHGRTW |
OrthoDBi | 652179at2759 |
PhylomeDBi | Q9Y3R4 |
TreeFami | TF331063 |
Family and domain databases
InterProi | View protein in InterPro IPR011040, Sialidase IPR026945, Sialidase-2 IPR026856, Sialidase_fam IPR036278, Sialidase_sf |
PANTHERi | PTHR10628, PTHR10628, 1 hit PTHR10628:SF6, PTHR10628:SF6, 1 hit |
Pfami | View protein in Pfam PF13088, BNR_2, 1 hit |
SUPFAMi | SSF50939, SSF50939, 1 hit |
i Sequence
Sequence statusi: Complete.
Q9Y3R4-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MASLPVLQKE SVFQSGAHAY RIPALLYLPG QQSLLAFAEQ RASKKDEHAE
60 70 80 90 100
LIVLRRGDYD APTHQVQWQA QEVVAQARLD GHRSMNPCPL YDAQTGTLFL
110 120 130 140 150
FFIAIPGQVT EQQQLQTRAN VTRLCQVTST DHGRTWSSPR DLTDAAIGPA
160 170 180 190 200
YREWSTFAVG PGHCLQLHDR ARSLVVPAYA YRKLHPIQRP IPSAFCFLSH
210 220 230 240 250
DHGRTWARGH FVAQDTLECQ VAEVETGEQR VVTLNARSHL RARVQAQSTN
260 270 280 290 300
DGLDFQESQL VKKLVEPPPQ GCQGSVISFP SPRSGPGSPA QWLLYTHPTH
310 320 330 340 350
SWQRADLGAY LNPRPPAPEA WSEPVLLAKG SCAYSDLQSM GTGPDGSPLF
360 370 380
GCLYEANDYE EIVFLMFTLK QAFPAEYLPQ
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_024461 | 11 | S → R. Corresponds to variant dbSNP:rs2233384Ensembl. | 1 | |
Natural variantiVAR_024462 | 41 | R → Q Reduced activity; increased sensitivity to inhibition by oseltamivir carboxylate. 1 PublicationCorresponds to variant dbSNP:rs2233385Ensembl. | 1 | |
Natural variantiVAR_049204 | 145 | A → T. Corresponds to variant dbSNP:rs2233390Ensembl. | 1 | |
Natural variantiVAR_055311 | 168 | H → N2 PublicationsCorresponds to variant dbSNP:rs2233391Ensembl. | 1 | |
Natural variantiVAR_055312 | 182 | R → Q. Corresponds to variant dbSNP:rs2233393Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | 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 |
CCDSi | CCDS2501.1 |
RefSeqi | NP_005374.2, NM_005383.2 |
Genome annotation databases
Ensembli | ENST00000233840; ENSP00000233840; ENSG00000115488 |
GeneIDi | 4759 |
KEGGi | hsa:4759 |
UCSCi | uc010zmn.2, human |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | 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 |
CCDSi | CCDS2501.1 |
RefSeqi | NP_005374.2, NM_005383.2 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1SNT | X-ray | 1.75 | A | 1-380 | [»] | |
1SO7 | X-ray | 1.49 | A | 1-380 | [»] | |
1VCU | X-ray | 2.85 | A/B | 1-380 | [»] | |
2F0Z | X-ray | 2.80 | A | 1-380 | [»] | |
2F10 | X-ray | 2.90 | A | 1-380 | [»] | |
2F11 | X-ray | 2.57 | A | 1-380 | [»] | |
2F12 | X-ray | 2.27 | A | 1-380 | [»] | |
2F13 | X-ray | 2.26 | A | 1-380 | [»] | |
2F24 | X-ray | 1.76 | A | 1-380 | [»] | |
2F25 | X-ray | 1.95 | A/B | 1-380 | [»] | |
2F26 | X-ray | 1.58 | A | 1-380 | [»] | |
2F27 | X-ray | 2.15 | A/B | 1-380 | [»] | |
2F28 | X-ray | 1.67 | A | 1-380 | [»] | |
2F29 | X-ray | 2.92 | A/B | 1-380 | [»] | |
4NC5 | X-ray | 2.51 | A | 1-380 | [»] | |
4NCS | X-ray | 2.20 | A | 1-380 | [»] | |
SMRi | Q9Y3R4 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 110832, 24 interactors |
IntActi | Q9Y3R4, 21 interactors |
STRINGi | 9606.ENSP00000233840 |
Chemistry databases
BindingDBi | Q9Y3R4 |
ChEMBLi | CHEMBL3200 |
DrugBanki | DB03991, 2-deoxy-2,3-dehydro-N-acetylneuraminic acid DB07960, 5-ACETAMIDO-5,6-DIHYDRO-4-HYDROXY-6-ISOBUTOXY-4H-PYRAN-2-CARBOXYLIC ACID DB00198, Oseltamivir DB00558, Zanamivir |
DrugCentrali | Q9Y3R4 |
SwissLipidsi | SLP:000001360 |
Protein family/group databases
CAZyi | GH33, Glycoside Hydrolase Family 33 |
PTM databases
iPTMneti | Q9Y3R4 |
PhosphoSitePlusi | Q9Y3R4 |
Genetic variation databases
BioMutai | NEU2 |
DMDMi | 229462907 |
Proteomic databases
MassIVEi | Q9Y3R4 |
PaxDbi | Q9Y3R4 |
PeptideAtlasi | Q9Y3R4 |
PRIDEi | Q9Y3R4 |
ProteomicsDBi | 86068 |
Protocols and materials databases
Antibodypediai | 34447, 258 antibodies |
Genome annotation databases
Ensembli | ENST00000233840; ENSP00000233840; ENSG00000115488 |
GeneIDi | 4759 |
KEGGi | hsa:4759 |
UCSCi | uc010zmn.2, human |
Organism-specific databases
CTDi | 4759 |
DisGeNETi | 4759 |
GeneCardsi | NEU2 |
HGNCi | HGNC:7759, NEU2 |
HPAi | ENSG00000115488, Tissue enriched (skin) |
MIMi | 605528, gene |
neXtProti | NX_Q9Y3R4 |
OpenTargetsi | ENSG00000115488 |
PharmGKBi | PA31561 |
VEuPathDBi | HostDB:ENSG00000115488.3 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502QSFT, Eukaryota |
GeneTreei | ENSGT00950000182944 |
HOGENOMi | CLU_024620_2_1_1 |
InParanoidi | Q9Y3R4 |
OMAi | HDHGRTW |
OrthoDBi | 652179at2759 |
PhylomeDBi | Q9Y3R4 |
TreeFami | TF331063 |
Enzyme and pathway databases
BRENDAi | 3.2.1.18, 2681 |
PathwayCommonsi | Q9Y3R4 |
Reactomei | R-HSA-1660662, Glycosphingolipid metabolism R-HSA-4085001, Sialic acid metabolism |
SABIO-RKi | Q9Y3R4 |
Miscellaneous databases
BioGRID-ORCSi | 4759, 2 hits in 875 CRISPR screens |
EvolutionaryTracei | Q9Y3R4 |
GeneWikii | NEU2 |
GenomeRNAii | 4759 |
Pharosi | Q9Y3R4, Tbio |
PROi | PR:Q9Y3R4 |
RNActi | Q9Y3R4, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000115488, Expressed in skin of leg and 13 other tissues |
Genevisiblei | Q9Y3R4, HS |
Family and domain databases
InterProi | View protein in InterPro IPR011040, Sialidase IPR026945, Sialidase-2 IPR026856, Sialidase_fam IPR036278, Sialidase_sf |
PANTHERi | PTHR10628, PTHR10628, 1 hit PTHR10628:SF6, PTHR10628:SF6, 1 hit |
Pfami | View protein in Pfam PF13088, BNR_2, 1 hit |
SUPFAMi | SSF50939, SSF50939, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | NEUR2_HUMAN | |
Accessioni | Q9Y3R4Primary (citable) accession number: Q9Y3R4 Secondary accession number(s): Q3KNW4, Q6NTB4 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 16, 2001 |
Last sequence update: | May 5, 2009 | |
Last modified: | February 10, 2021 | |
This is version 166 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human chromosome 2
Human chromosome 2: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Glycosyl hydrolases
Classification of glycosyl hydrolase families and list of entries