UniProtKB - Q8WWR8 (NEUR4_HUMAN)
Sialidase-4
NEU4
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. Efficiently hydrolyzes gangliosides including alpha-(2->3)-sialylated GD1a and GM3 and alpha-(2->8)-sialylated GD3 (PubMed:15847605, PubMed:21521691, PubMed:15213228).
Hydrolyzes poly-alpha-(2->8)-sialylated neural cell adhesion molecule NCAM1 likely at growth cones, suppressing neurite outgrowth in hippocampal neurons (By similarity).
May desialylate sialyl Lewis A and X antigens at the cell surface, down-regulating these glycan epitopes recognized by SELE/E selectin in the initiation of cell adhesion and extravasation (PubMed:21521691).
Has sialidase activity toward mucin, fetuin and sialyllactose (PubMed:15847605).
By similarity3 PublicationsCatalytic activityi
- ganglioside GM3 + H2O = β-D-galactosyl-(1→4)-β-D-glucosyl-(1↔1)-ceramide + N-acetylneuraminate1 PublicationThis reaction proceeds in the forward1 Publication direction.
- ganglioside GM3 (d18:1(4E)) + H2O = a β-D-Gal-(1→4)-β-D-Glc-(1↔1)-Cer(d18:1(4E)) + 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-acetylneuraminate1 PublicationThis 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 forward1 Publication direction.
- This reaction proceeds in the forward1 Publication 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.4 Publications EC:3.2.1.18
pH dependencei
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 23 | SubstrateBy similarity | 1 | |
Binding sitei | 43 | SubstrateBy similarity | 1 | |
Active sitei | 47 | Proton acceptorBy similarity | 1 | |
Active sitei | 48 | Proton acceptorBy similarity | 1 | |
Binding sitei | 177 | SubstrateBy similarity | 1 | |
Binding sitei | 179 | SubstrateBy similarity | 1 | |
Binding sitei | 222 | SubstrateBy similarity | 1 | |
Binding sitei | 242 | SubstrateBy similarity | 1 | |
Binding sitei | 389 | SubstrateBy similarity | 1 | |
Active sitei | 419 | NucleophileBy similarity | 1 | |
Active sitei | 440 | 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: UniProtKB
GO - Biological processi
- ganglioside catabolic process Source: UniProtKB
- glycoprotein catabolic process Source: UniProtKB
- negative regulation of neuron projection development Source: Ensembl
- 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 | Q8WWR8 |
Reactomei | R-HSA-1660662, Glycosphingolipid metabolism [Q8WWR8-2] R-HSA-4085001, Sialic acid metabolism |
SABIO-RKi | Q8WWR8 |
SignaLinki | Q8WWR8 |
Protein family/group databases
CAZyi | GH33, Glycoside Hydrolase Family 33 |
Chemistry databases
SwissLipidsi | SLP:000001400 [Q8WWR8-2] SLP:000001401 [Q8WWR8-1] |
Names & Taxonomyi
Protein namesi | Recommended name: Sialidase-4 (EC:3.2.1.184 Publications)Alternative name(s): N-acetyl-alpha-neuraminidase 4 |
Gene namesi | Name:NEU4 ORF Names:LP5125 |
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:21328, NEU4 |
MIMi | 608527, gene |
neXtProti | NX_Q8WWR8 |
VEuPathDBi | HostDB:ENSG00000204099 |
Subcellular locationi
Mitochondrion
- Mitochondrion membrane 2 Publications; Peripheral membrane protein
Plasma membrane
- Cell membrane 1 Publication; Peripheral membrane protein
Endoplasmic reticulum
- Endoplasmic reticulum membrane 1 Publication; Peripheral membrane protein
- Microsome membrane 1 Publication; Peripheral membrane protein
Other locations
- neuron projection By similarity
Note: Predominantly associates with endoplasmic reticulum membranes. Only a small fraction associates with mitochondrial and plasma membranes.2 Publications
Mitochondrion
- Mitochondrion inner membrane 1 Publication; Peripheral membrane protein
- Mitochondrion outer membrane 2 Publications; Peripheral membrane protein
Lysosome
- Lysosome lumen 1 Publication
Note: According to PubMed:15213228, 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.
Endoplasmic reticulum
- endoplasmic reticulum membrane Source: UniProtKB
Lysosome
- lysosomal lumen Source: Reactome
- lysosome Source: UniProtKB
Mitochondrion
- mitochondrial inner membrane Source: UniProtKB
- mitochondrial outer membrane Source: UniProtKB
Plasma Membrane
- plasma membrane Source: UniProtKB-SubCell
Other locations
- cytoplasm Source: GO_Central
- intracellular membrane-bounded organelle Source: GO_Central
- membrane Source: GO_Central
- neuron projection Source: UniProtKB-SubCell
- organelle inner membrane Source: UniProtKB
Keywords - Cellular componenti
Cell membrane, Cell projection, Endoplasmic reticulum, Lysosome, Membrane, Microsome, Mitochondrion, Mitochondrion inner membrane, Mitochondrion outer membranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 5 | R → A: Impairs mitochondrial targeting. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 129807 |
OpenTargetsi | ENSG00000204099 |
PharmGKBi | PA134917116 |
Miscellaneous databases
Pharosi | Q8WWR8, Tchem |
Chemistry databases
ChEMBLi | CHEMBL4174 |
Genetic variation databases
BioMutai | NEU4 |
DMDMi | 90110434 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000208906 | 1 – 484 | Sialidase-4Add BLAST | 484 |
Post-translational modificationi
Proteomic databases
MassIVEi | Q8WWR8 |
PaxDbi | Q8WWR8 |
PeptideAtlasi | Q8WWR8 |
PRIDEi | Q8WWR8 |
ProteomicsDBi | 74925 [Q8WWR8-1] 74926 [Q8WWR8-2] |
PTM databases
GlyGeni | Q8WWR8, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | Q8WWR8 |
PhosphoSitePlusi | Q8WWR8 |
Expressioni
Tissue specificityi
Inductioni
Gene expression databases
Bgeei | ENSG00000204099, Expressed in right lobe of liver and 155 other tissues |
ExpressionAtlasi | Q8WWR8, baseline and differential |
Genevisiblei | Q8WWR8, HS |
Organism-specific databases
HPAi | ENSG00000204099, Tissue enriched (liver) |
Interactioni
Binary interactionsi
Q8WWR8
With | #Exp. | IntAct |
---|---|---|
MDFI [Q99750] | 4 | EBI-746964,EBI-724076 |
PLSCR1 [O15162] | 2 | EBI-746964,EBI-740019 |
Isoform 2 [Q8WWR8-2]
Protein-protein interaction databases
BioGRIDi | 126209, 63 interactors |
IntActi | Q8WWR8, 23 interactors |
MINTi | Q8WWR8 |
STRINGi | 9606.ENSP00000320318 |
Chemistry databases
BindingDBi | Q8WWR8 |
Miscellaneous databases
RNActi | Q8WWR8, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Repeati | 127 – 138 | BNR 1Add BLAST | 12 | |
Repeati | 200 – 211 | BNR 2Add BLAST | 12 | |
Repeati | 251 – 262 | BNR 3Add BLAST | 12 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 284 – 357 | DisorderedSequence analysisAdd BLAST | 74 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 22 – 25 | FRIP motif | 4 |
Sequence similaritiesi
Keywords - Domaini
RepeatPhylogenomic databases
eggNOGi | ENOG502QSFT, Eukaryota |
GeneTreei | ENSGT00950000182944 |
InParanoidi | Q8WWR8 |
OMAi | GRTWHCG |
PhylomeDBi | Q8WWR8 |
TreeFami | TF331063 |
Family and domain databases
InterProi | View protein in InterPro IPR011040, Sialidase IPR026946, Sialidase-4 IPR026856, Sialidase_fam IPR036278, Sialidase_sf |
PANTHERi | PTHR10628, PTHR10628, 1 hit PTHR10628:SF22, PTHR10628:SF22, 1 hit |
Pfami | View protein in Pfam PF13088, BNR_2, 1 hit |
SUPFAMi | SSF50939, SSF50939, 1 hit |
s (3+)i Sequence
Sequence statusi: Complete.
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 8 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
MGVPRTPSRT VLFERERTGL TYRVPSLLPV PPGPTLLAFV EQRLSPDDSH
60 70 80 90 100
AHRLVLRRGT LAGGSVRWGA LHVLGTAALA EHRSMNPCPV HDAGTGTVFL
110 120 130 140 150
FFIAVLGHTP EAVQIATGRN AARLCCVASR DAGLSWGSAR DLTEEAIGGA
160 170 180 190 200
VQDWATFAVG PGHGVQLPSG RLLVPAYTYR VDRRECFGKI CRTSPHSFAF
210 220 230 240 250
YSDDHGRTWR CGGLVPNLRS GECQLAAVDG GQAGSFLYCN ARSPLGSRVQ
260 270 280 290 300
ALSTDEGTSF LPAERVASLP ETAWGCQGSI VGFPAPAPNR PRDDSWSVGP
310 320 330 340 350
GSPLQPPLLG PGVHEPPEEA AVDPRGGQVP GGPFSRLQPR GDGPRQPGPR
360 370 380 390 400
PGVSGDVGSW TLALPMPFAA PPQSPTWLLY SHPVGRRARL HMGIRLSQSP
410 420 430 440 450
LDPRSWTEPW VIYEGPSGYS DLASIGPAPE GGLVFACLYE SGARTSYDEI
460 470 480
SFCTFSLREV LENVPASPKP PNLGDKPRGC CWPS
Computationally mapped potential isoform sequencesi
There are 8 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketC9JRN9 | C9JRN9_HUMAN | Exo-alpha-sialidase | NEU4 | 260 | Annotation score: | ||
C9J5X2 | C9J5X2_HUMAN | Exo-alpha-sialidase | NEU4 | 188 | Annotation score: | ||
F8WE58 | F8WE58_HUMAN | Exo-alpha-sialidase | NEU4 | 158 | Annotation score: | ||
C9J2R4 | C9J2R4_HUMAN | Sialidase-4 | NEU4 | 214 | Annotation score: | ||
C9J2V4 | C9J2V4_HUMAN | Sialidase-4 | NEU4 | 77 | Annotation score: | ||
C9IZG9 | C9IZG9_HUMAN | Sialidase-4 | NEU4 | 214 | Annotation score: | ||
C9JEA3 | C9JEA3_HUMAN | Sialidase-4 | NEU4 | 144 | Annotation score: | ||
C9J295 | C9J295_HUMAN | Sialidase-4 | NEU4 | 52 | Annotation score: |
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 184 | R → L in CAC81904 (PubMed:14962670).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_067458 | 301 | G → R3 PublicationsCorresponds to variant dbSNP:rs11545301Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_037491 | 1 | M → MMSSAAFPRWLSM in isoform 2. 1 Publication | 1 | |
Alternative sequenceiVSP_047123 | 1 | M → MMSSAAFPRWLQSM in isoform 3. Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | 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 |
CCDSi | CCDS2553.1 [Q8WWR8-2] CCDS54441.1 [Q8WWR8-3] CCDS54442.1 [Q8WWR8-1] |
RefSeqi | NP_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] |
Genome annotation databases
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | 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 |
CCDSi | CCDS2553.1 [Q8WWR8-2] CCDS54441.1 [Q8WWR8-3] CCDS54442.1 [Q8WWR8-1] |
RefSeqi | NP_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] |
3D structure databases
AlphaFoldDBi | Q8WWR8 |
SMRi | Q8WWR8 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 126209, 63 interactors |
IntActi | Q8WWR8, 23 interactors |
MINTi | Q8WWR8 |
STRINGi | 9606.ENSP00000320318 |
Chemistry databases
BindingDBi | Q8WWR8 |
ChEMBLi | CHEMBL4174 |
SwissLipidsi | SLP:000001400 [Q8WWR8-2] SLP:000001401 [Q8WWR8-1] |
Protein family/group databases
CAZyi | GH33, Glycoside Hydrolase Family 33 |
PTM databases
GlyGeni | Q8WWR8, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | Q8WWR8 |
PhosphoSitePlusi | Q8WWR8 |
Genetic variation databases
BioMutai | NEU4 |
DMDMi | 90110434 |
Proteomic databases
MassIVEi | Q8WWR8 |
PaxDbi | Q8WWR8 |
PeptideAtlasi | Q8WWR8 |
PRIDEi | Q8WWR8 |
ProteomicsDBi | 74925 [Q8WWR8-1] 74926 [Q8WWR8-2] |
Protocols and materials databases
Antibodypediai | 34580, 171 antibodies from 25 providers |
DNASUi | 129807 |
Genome annotation databases
Organism-specific databases
CTDi | 129807 |
DisGeNETi | 129807 |
GeneCardsi | NEU4 |
HGNCi | HGNC:21328, NEU4 |
HPAi | ENSG00000204099, Tissue enriched (liver) |
MIMi | 608527, gene |
neXtProti | NX_Q8WWR8 |
OpenTargetsi | ENSG00000204099 |
PharmGKBi | PA134917116 |
VEuPathDBi | HostDB:ENSG00000204099 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502QSFT, Eukaryota |
GeneTreei | ENSGT00950000182944 |
InParanoidi | Q8WWR8 |
OMAi | GRTWHCG |
PhylomeDBi | Q8WWR8 |
TreeFami | TF331063 |
Enzyme and pathway databases
BRENDAi | 3.2.1.18, 2681 |
PathwayCommonsi | Q8WWR8 |
Reactomei | R-HSA-1660662, Glycosphingolipid metabolism [Q8WWR8-2] R-HSA-4085001, Sialic acid metabolism |
SABIO-RKi | Q8WWR8 |
SignaLinki | Q8WWR8 |
Miscellaneous databases
BioGRID-ORCSi | 129807, 12 hits in 1069 CRISPR screens |
GeneWikii | NEU4 |
GenomeRNAii | 129807 |
Pharosi | Q8WWR8, Tchem |
PROi | PR:Q8WWR8 |
RNActi | Q8WWR8, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000204099, Expressed in right lobe of liver and 155 other tissues |
ExpressionAtlasi | Q8WWR8, baseline and differential |
Genevisiblei | Q8WWR8, HS |
Family and domain databases
InterProi | View protein in InterPro IPR011040, Sialidase IPR026946, Sialidase-4 IPR026856, Sialidase_fam IPR036278, Sialidase_sf |
PANTHERi | PTHR10628, PTHR10628, 1 hit PTHR10628:SF22, PTHR10628:SF22, 1 hit |
Pfami | View protein in Pfam PF13088, BNR_2, 1 hit |
SUPFAMi | SSF50939, SSF50939, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | NEUR4_HUMAN | |
Accessioni | Q8WWR8Primary (citable) accession number: Q8WWR8 Secondary accession number(s): A8K056, J3KNJ5, Q96D64 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | June 7, 2004 |
Last sequence update: | March 7, 2006 | |
Last modified: | May 25, 2022 | |
This is version 169 of the entry and version 3 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 2
Human chromosome 2: 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