UniProtKB - Q9UQ49 (NEUR3_HUMAN)
Sialidase-3
NEU3
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. Displays high catalytic efficiency for gangliosides including alpha-(2->3)-sialylated GD1a and GM3 and alpha-(2->8)-sialylated GD3 (PubMed:11298736, PubMed:15847605, PubMed:10861246, PubMed:20511247, PubMed:28646141, PubMed:10405317, PubMed:12011038).
Plays a role in the regulation of transmembrane signaling through the modulation of ganglioside content of the lipid bilayer and by direct interaction with signaling receptors, such as EGFR (PubMed:17334392, PubMed:25922362).
Desialylates EGFR and activates downstream signaling in proliferating cells (PubMed:25922362).
Contributes to clathrin-mediated endocytosis by regulating sorting of endocytosed receptors to early and recycling endosomes (PubMed:26251452).
10 PublicationsCatalytic activityi
- This reaction proceeds in the forward4 Publications direction.
- ganglioside GD1a (d18:1(4E)) + H2O = ganglioside GM1 (d18:1(4E)) + N-acetylneuraminate3 PublicationsThis reaction proceeds in the forward3 Publications direction.
- This reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forward3 Publications direction.
- This reaction proceeds in the forward3 Publications direction.
- ganglioside GM3 + H2O = β-D-galactosyl-(1→4)-β-D-glucosyl-(1↔1)-ceramide + N-acetylneuraminate3 PublicationsThis reaction proceeds in the forward3 Publications direction.
- This reaction proceeds in the forwardBy similarity direction.
- This reaction proceeds in the forwardBy similarity direction.
- This reaction proceeds in the forwardBy similarity direction.
- ganglioside GM3 (d18:1(4E)) + H2O = a β-D-Gal-(1→4)-β-D-Glc-(1↔1)-Cer(d18:1(4E)) + N-acetylneuraminate3 PublicationsThis reaction proceeds in the forward3 Publications direction.
- This reaction proceeds in the forwardBy similarity 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.6 Publications EC:3.2.1.18
Kineticsi
- KM=47 µM for ganglioside GD1a1 Publication
pH dependencei
Temperature dependencei
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 25 | SubstrateBy similarity | 1 | |
Binding sitei | 45 | SubstrateCurated | 1 | |
Active sitei | 50 | Proton acceptor1 Publication | 1 | |
Binding sitei | 179 | SubstrateCurated | 1 | |
Binding sitei | 181 | SubstrateCurated | 1 | |
Binding sitei | 225 | SubstrateCurated | 1 | |
Binding sitei | 245 | SubstrateCurated | 1 | |
Binding sitei | 340 | SubstrateCurated | 1 | |
Active sitei | 370 | Nucleophile1 Publication | 1 | |
Active sitei | 387 | Sequence analysis | 1 |
GO - Molecular functioni
- alpha-sialidase activity Source: MGI
- 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: UniProtKB
GO - Biological processi
- carbohydrate metabolic process Source: MGI
- ganglioside catabolic process Source: UniProtKB
- glycosphingolipid metabolic process Source: Reactome
- negative regulation of clathrin-dependent endocytosis Source: UniProtKB
- oligosaccharide catabolic process Source: UniProtKB
- positive regulation of epidermal growth factor receptor signaling pathway 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 | Q9UQ49 |
Reactomei | R-HSA-1660662, Glycosphingolipid metabolism R-HSA-4085001, Sialic acid metabolism |
SABIO-RKi | Q9UQ49 |
SignaLinki | Q9UQ49 |
Protein family/group databases
CAZyi | GH33, Glycoside Hydrolase Family 33 |
Chemistry databases
SwissLipidsi | SLP:000001372 [Q9UQ49-1] |
Names & Taxonomyi
Protein namesi | Recommended name: Sialidase-3 (EC:3.2.1.186 Publications)Alternative name(s): Ganglioside sialidasedis Membrane sialidase N-acetyl-alpha-neuraminidase 3 |
Gene namesi | Name:NEU3 |
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:7760, NEU3 |
MIMi | 604617, gene |
neXtProti | NX_Q9UQ49 |
VEuPathDBi | HostDB:ENSG00000162139 |
Subcellular locationi
Plasma membrane
- Cell membrane 4 Publications; Peripheral membrane protein 2 Publications
Lysosome
- Lysosome membrane 1 Publication; Peripheral membrane protein 1 Publication
Endosome
- Early endosome membrane 1 Publication; Peripheral membrane protein 1 Publication
- Recycling endosome membrane 1 Publication; Peripheral membrane protein 1 Publication
Other locations
- caveola 1 Publication
Note: Associates with the external leaflet of the plasma membrane (By similarity). S-acylated NEU3 likely spans the lipid bilayer with a portion of C-terminus exposed to the cytosol and the catalytic region facing the extracellular space (PubMed:28646141).By similarity1 Publication
Endosome
- early endosome membrane Source: UniProtKB
- recycling endosome membrane Source: UniProtKB
Lysosome
- lysosomal membrane Source: UniProtKB
Plasma Membrane
- caveola Source: UniProtKB-SubCell
- external side of plasma membrane Source: Ensembl
- plasma membrane Source: UniProtKB
Other locations
- cytoplasm Source: GO_Central
- intracellular membrane-bounded organelle Source: GO_Central
- membrane Source: GO_Central
Keywords - Cellular componenti
Cell membrane, Endosome, Lysosome, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 25 | R → H: Loss of enzyme activity. 1 Publication | 1 | |
Mutagenesisi | 45 | R → V: Loss of enzyme activity. 1 Publication | 1 | |
Mutagenesisi | 50 | D → S or A: Nearly abolishes enzyme activity. 2 Publications | 1 | |
Mutagenesisi | 51 | E → D: Decreases enzyme activity. 1 Publication | 1 | |
Mutagenesisi | 88 | N → D: Markedly decreases enzyme activity. 1 Publication | 1 | |
Mutagenesisi | 107 | V → M: Markedly decreases enzyme activity. 1 Publication | 1 | |
Mutagenesisi | 114 | R → Q: Decreases enzyme activity. 1 Publication | 1 | |
Mutagenesisi | 162 | G → A: Markedly decreases enzyme activity. 1 Publication | 1 | |
Mutagenesisi | 179 | Y → F: Loss of enzyme activity. 1 Publication | 1 | |
Mutagenesisi | 181 | Y → A: Markedly decreases the recruitment within caveola. 1 Publication | 1 | |
Mutagenesisi | 181 | Y → F: Nearly abolishes enzyme activity. 1 Publication | 1 | |
Mutagenesisi | 187 | F → R: Decreases the recruitment within caveola. 1 Publication | 1 | |
Mutagenesisi | 225 | E → S: Loss of enzyme activity. 1 Publication | 1 | |
Mutagenesisi | 245 | R → A: Loss of enzyme activity. 1 Publication | 1 | |
Mutagenesisi | 340 | R → A: Loss of enzyme activity. 1 Publication | 1 | |
Mutagenesisi | 370 | Y → F or C: Loss of enzyme activity. 3 Publications | 1 |
Organism-specific databases
DisGeNETi | 10825 |
OpenTargetsi | ENSG00000162139 |
PharmGKBi | PA31562 |
Miscellaneous databases
Pharosi | Q9UQ49, Tbio |
Chemistry databases
ChEMBLi | CHEMBL3046 |
DrugCentrali | Q9UQ49 |
Genetic variation databases
BioMutai | NEU3 |
DMDMi | 17369720 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000208903 | 1 – 428 | Sialidase-3Add BLAST | 428 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 313 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Lipoprotein, PhosphoproteinProteomic databases
EPDi | Q9UQ49 |
jPOSTi | Q9UQ49 |
MassIVEi | Q9UQ49 |
MaxQBi | Q9UQ49 |
PaxDbi | Q9UQ49 |
PeptideAtlasi | Q9UQ49 |
PRIDEi | Q9UQ49 |
ProteomicsDBi | 1854 85507 [Q9UQ49-1] |
PTM databases
iPTMneti | Q9UQ49 |
PhosphoSitePlusi | Q9UQ49 |
SwissPalmi | Q9UQ49 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000162139, Expressed in quadriceps femoris and 174 other tissues |
ExpressionAtlasi | Q9UQ49, baseline and differential |
Genevisiblei | Q9UQ49, HS |
Organism-specific databases
HPAi | ENSG00000162139, Low tissue specificity |
Interactioni
Subunit structurei
Protein-protein interaction databases
BioGRIDi | 116038, 16 interactors |
IntActi | Q9UQ49, 2 interactors |
STRINGi | 9606.ENSP00000294064 |
Chemistry databases
BindingDBi | Q9UQ49 |
Miscellaneous databases
RNActi | Q9UQ49, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Repeati | 129 – 140 | BNR 1Add BLAST | 12 | |
Repeati | 203 – 214 | BNR 2Add BLAST | 12 | |
Repeati | 254 – 265 | BNR 3Add BLAST | 12 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 294 – 318 | DisorderedSequence analysisAdd BLAST | 25 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 24 – 27 | FRIP motif | 4 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 298 – 316 | Polar residuesSequence analysisAdd BLAST | 19 |
Sequence similaritiesi
Keywords - Domaini
RepeatPhylogenomic databases
eggNOGi | ENOG502QSFT, Eukaryota |
GeneTreei | ENSGT00950000182944 |
HOGENOMi | CLU_024620_2_0_1 |
InParanoidi | Q9UQ49 |
OMAi | YTYYIPY |
PhylomeDBi | Q9UQ49 |
TreeFami | TF331063 |
Family and domain databases
InterProi | View protein in InterPro IPR011040, Sialidase IPR026944, Sialidase-3 IPR026856, Sialidase_fam IPR036278, Sialidase_sf |
PANTHERi | PTHR10628, PTHR10628, 1 hit PTHR10628:SF23, PTHR10628:SF23, 1 hit |
Pfami | View protein in Pfam PF13088, BNR_2, 1 hit |
SUPFAMi | SSF50939, SSF50939, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MEEVTTCSFN SPLFRQEDDR GITYRIPALL YIPPTHTFLA FAEKRSTRRD
60 70 80 90 100
EDALHLVLRR GLRIGQLVQW GPLKPLMEAT LPGHRTMNPC PVWEQKSGCV
110 120 130 140 150
FLFFICVRGH VTERQQIVSG RNAARLCFIY SQDAGCSWSE VRDLTEEVIG
160 170 180 190 200
SELKHWATFA VGPGHGIQLQ SGRLVIPAYT YYIPSWFFCF QLPCKTRPHS
210 220 230 240 250
LMIYSDDLGV TWHHGRLIRP MVTVECEVAE VTGRAGHPVL YCSARTPNRC
260 270 280 290 300
RAEALSTDHG EGFQRLALSR QLCEPPHGCQ GSVVSFRPLE IPHRCQDSSS
310 320 330 340 350
KDAPTIQQSS PGSSLRLEEE AGTPSESWLL YSHPTSRKQR VDLGIYLNQT
360 370 380 390 400
PLEAACWSRP WILHCGPCGY SDLAALEEEG LFGCLFECGT KQECEQIAFR
410 420
LFTHREILSH LQGDCTSPGR NPSQFKSN
Computationally mapped potential isoform sequencesi
There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketE9PNK1 | E9PNK1_HUMAN | Sialidase-3 | NEU3 | 170 | Annotation score: | ||
E9PR25 | E9PR25_HUMAN | Sialidase-3 | NEU3 | 139 | Annotation score: | ||
E9PI40 | E9PI40_HUMAN | Sialidase-3 | NEU3 | 58 | Annotation score: | ||
E9PMZ3 | E9PMZ3_HUMAN | Sialidase-3 | NEU3 | 101 | Annotation score: |
Sequence cautioni
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_055839 | 15 | R → Q. Corresponds to variant dbSNP:rs7115499Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_054145 | 1 | M → MRPADLPPRPMEESPASSSA PTETEEPGSSAEVM in isoform 2. 2 Publications | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB008185 mRNA Translation: BAA82611.1 Y18563 mRNA Translation: CAB96131.1 Different initiation. AK022450 mRNA Translation: BAG51074.1 AK290442 mRNA Translation: BAF83131.1 AP001992 Genomic DNA No translation available. CH471076 Genomic DNA Translation: EAW74953.1 BC136397 mRNA Translation: AAI36398.1 BC144059 mRNA Translation: AAI44060.1 |
CCDSi | CCDS44682.1 [Q9UQ49-2] |
RefSeqi | NP_006647.3, NM_006656.5 [Q9UQ49-2] |
Genome annotation databases
Ensembli | ENST00000294064; ENSP00000294064; ENSG00000162139 [Q9UQ49-2] ENST00000531509; ENSP00000432097; ENSG00000162139 [Q9UQ49-2] |
GeneIDi | 10825 |
KEGGi | hsa:10825 |
MANE-Selecti | ENST00000294064.9; ENSP00000294064.4; NM_006656.6; NP_006647.3 [Q9UQ49-2] |
UCSCi | uc001ovw.4, human [Q9UQ49-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Web resourcesi
Atlas of Genetics and Cytogenetics in Oncology and Haematology |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB008185 mRNA Translation: BAA82611.1 Y18563 mRNA Translation: CAB96131.1 Different initiation. AK022450 mRNA Translation: BAG51074.1 AK290442 mRNA Translation: BAF83131.1 AP001992 Genomic DNA No translation available. CH471076 Genomic DNA Translation: EAW74953.1 BC136397 mRNA Translation: AAI36398.1 BC144059 mRNA Translation: AAI44060.1 |
CCDSi | CCDS44682.1 [Q9UQ49-2] |
RefSeqi | NP_006647.3, NM_006656.5 [Q9UQ49-2] |
3D structure databases
SMRi | Q9UQ49 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 116038, 16 interactors |
IntActi | Q9UQ49, 2 interactors |
STRINGi | 9606.ENSP00000294064 |
Chemistry databases
BindingDBi | Q9UQ49 |
ChEMBLi | CHEMBL3046 |
DrugCentrali | Q9UQ49 |
SwissLipidsi | SLP:000001372 [Q9UQ49-1] |
Protein family/group databases
CAZyi | GH33, Glycoside Hydrolase Family 33 |
PTM databases
iPTMneti | Q9UQ49 |
PhosphoSitePlusi | Q9UQ49 |
SwissPalmi | Q9UQ49 |
Genetic variation databases
BioMutai | NEU3 |
DMDMi | 17369720 |
Proteomic databases
EPDi | Q9UQ49 |
jPOSTi | Q9UQ49 |
MassIVEi | Q9UQ49 |
MaxQBi | Q9UQ49 |
PaxDbi | Q9UQ49 |
PeptideAtlasi | Q9UQ49 |
PRIDEi | Q9UQ49 |
ProteomicsDBi | 1854 85507 [Q9UQ49-1] |
Protocols and materials databases
Antibodypediai | 56317, 76 antibodies from 14 providers |
DNASUi | 10825 |
Genome annotation databases
Ensembli | ENST00000294064; ENSP00000294064; ENSG00000162139 [Q9UQ49-2] ENST00000531509; ENSP00000432097; ENSG00000162139 [Q9UQ49-2] |
GeneIDi | 10825 |
KEGGi | hsa:10825 |
MANE-Selecti | ENST00000294064.9; ENSP00000294064.4; NM_006656.6; NP_006647.3 [Q9UQ49-2] |
UCSCi | uc001ovw.4, human [Q9UQ49-1] |
Organism-specific databases
CTDi | 10825 |
DisGeNETi | 10825 |
GeneCardsi | NEU3 |
HGNCi | HGNC:7760, NEU3 |
HPAi | ENSG00000162139, Low tissue specificity |
MIMi | 604617, gene |
neXtProti | NX_Q9UQ49 |
OpenTargetsi | ENSG00000162139 |
PharmGKBi | PA31562 |
VEuPathDBi | HostDB:ENSG00000162139 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502QSFT, Eukaryota |
GeneTreei | ENSGT00950000182944 |
HOGENOMi | CLU_024620_2_0_1 |
InParanoidi | Q9UQ49 |
OMAi | YTYYIPY |
PhylomeDBi | Q9UQ49 |
TreeFami | TF331063 |
Enzyme and pathway databases
BRENDAi | 3.2.1.18, 2681 |
PathwayCommonsi | Q9UQ49 |
Reactomei | R-HSA-1660662, Glycosphingolipid metabolism R-HSA-4085001, Sialic acid metabolism |
SABIO-RKi | Q9UQ49 |
SignaLinki | Q9UQ49 |
Miscellaneous databases
BioGRID-ORCSi | 10825, 10 hits in 1048 CRISPR screens |
ChiTaRSi | NEU3, human |
GeneWikii | NEU3 |
GenomeRNAii | 10825 |
Pharosi | Q9UQ49, Tbio |
PROi | PR:Q9UQ49 |
RNActi | Q9UQ49, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000162139, Expressed in quadriceps femoris and 174 other tissues |
ExpressionAtlasi | Q9UQ49, baseline and differential |
Genevisiblei | Q9UQ49, HS |
Family and domain databases
InterProi | View protein in InterPro IPR011040, Sialidase IPR026944, Sialidase-3 IPR026856, Sialidase_fam IPR036278, Sialidase_sf |
PANTHERi | PTHR10628, PTHR10628, 1 hit PTHR10628:SF23, PTHR10628:SF23, 1 hit |
Pfami | View protein in Pfam PF13088, BNR_2, 1 hit |
SUPFAMi | SSF50939, SSF50939, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | NEUR3_HUMAN | |
Accessioni | Q9UQ49Primary (citable) accession number: Q9UQ49 Secondary accession number(s): A8K327, Q9NQE1 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 16, 2001 |
Last sequence update: | May 1, 2000 | |
Last modified: | February 23, 2022 | |
This is version 166 of the entry and version 1 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
Reference proteomeDocuments
- Glycosyl hydrolases
Classification of glycosyl hydrolase families and list of entries - Human chromosome 11
Human chromosome 11: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - 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 - SIMILARITY comments
Index of protein domains and families