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Protein

Sialidase-4

Gene

NEU4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.2 Publications

Catalytic activityi

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.1 Publication

pH dependencei

Optimum pH is 3.2.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei23SubstrateBy similarity1
Binding sitei43SubstrateBy similarity1
Active sitei47Proton acceptorBy similarity1
Active sitei48Proton acceptorBy similarity1
Binding sitei177SubstrateBy similarity1
Binding sitei179SubstrateBy similarity1
Binding sitei222SubstrateBy similarity1
Binding sitei242SubstrateBy similarity1
Binding sitei389SubstrateBy similarity1
Active sitei419NucleophileBy similarity1
Active sitei440Sequence analysis1

GO - Molecular functioni

GO - Biological processi

  • ganglioside catabolic process Source: UniProtKB
  • glycoprotein catabolic process Source: UniProtKB
  • glycosphingolipid metabolic process Source: Reactome
  • oligosaccharide catabolic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Glycosidase, Hydrolase

Keywords - Biological processi

Carbohydrate metabolism, Lipid degradation, Lipid metabolism

Enzyme and pathway databases

BioCyciZFISH:HS11296-MONOMER.
BRENDAi3.2.1.18. 2681.
ReactomeiR-HSA-1660662. Glycosphingolipid metabolism.
R-HSA-4085001. Sialic acid metabolism.
SABIO-RKQ8WWR8.

Protein family/group databases

CAZyiGH33. Glycoside Hydrolase Family 33.

Chemistry databases

SwissLipidsiSLP:000001400. [Q8WWR8-2]
SLP:000001401. [Q8WWR8-1]

Names & Taxonomyi

Protein namesi
Recommended name:
Sialidase-4 (EC:3.2.1.18)
Alternative name(s):
N-acetyl-alpha-neuraminidase 4
Gene namesi
Name:NEU4
ORF Names:LP5125
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:21328. NEU4.

Subcellular locationi

Isoform 2 :
  • Lysosome lumen

  • 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.

GO - Cellular componenti

  • lysosomal lumen Source: Reactome
  • lysosome Source: UniProtKB
  • mitochondrion Source: Ensembl
  • organelle inner membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Lysosome, Membrane

Pathology & Biotechi

Organism-specific databases

OpenTargetsiENSG00000204099.
ENSG00000277926.
PharmGKBiPA134917116.

Chemistry databases

ChEMBLiCHEMBL4174.

Polymorphism and mutation databases

BioMutaiNEU4.
DMDMi90110434.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002089061 – 484Sialidase-4Add BLAST484

Post-translational modificationi

According to PubMed:15213228, phosphorylation of mannose residues may ensure efficient transport of isoform 2 to the lysosomes via the mannose 6-phosphate receptor.
Isoform 2 is glycosylated.1 Publication

Proteomic databases

PaxDbiQ8WWR8.
PRIDEiQ8WWR8.

PTM databases

iPTMnetiQ8WWR8.
PhosphoSitePlusiQ8WWR8.

Expressioni

Tissue specificityi

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

Inductioni

Down-regulated during monocyte to macrophage differentiation.1 Publication

Gene expression databases

BgeeiENSG00000204099.
CleanExiHS_NEU4.
ExpressionAtlasiQ8WWR8. baseline and differential.
GenevisibleiQ8WWR8. HS.

Organism-specific databases

HPAiHPA037394.
HPA037395.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
AP2B1P630103EBI-10277551,EBI-432924
MDFIQ997504EBI-746964,EBI-724076
PLSCR1O151622EBI-746964,EBI-740019
TCF4P158843EBI-10277551,EBI-533224
TRIP6Q156543EBI-10277551,EBI-742327

Protein-protein interaction databases

BioGridi126209. 19 interactors.
IntActiQ8WWR8. 9 interactors.
MINTiMINT-1447950.
STRINGi9606.ENSP00000320318.

Chemistry databases

BindingDBiQ8WWR8.

Structurei

3D structure databases

ProteinModelPortaliQ8WWR8.
SMRiQ8WWR8.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati127 – 138BNR 1Add BLAST12
Repeati200 – 211BNR 2Add BLAST12
Repeati251 – 262BNR 3Add BLAST12

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi22 – 25FRIP motif4

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi284 – 375Pro-richAdd BLAST92

Sequence similaritiesi

Belongs to the glycosyl hydrolase 33 family.Curated
Contains 3 BNR repeats.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG410IFVF. Eukaryota.
ENOG410Y74Z. LUCA.
GeneTreeiENSGT00390000011171.
HOGENOMiHOG000233778.
HOVERGENiHBG052608.
InParanoidiQ8WWR8.
KOiK12357.
OMAiHIDCKEC.
OrthoDBiEOG091G08BI.
PhylomeDBiQ8WWR8.
TreeFamiTF331063.

Family and domain databases

Gene3Di2.120.10.10. 2 hits.
InterProiIPR026946. Sialidase-4.
IPR026856. Sialidase_fam.
IPR011040. Sialidases.
[Graphical view]
PANTHERiPTHR10628. PTHR10628. 2 hits.
PTHR10628:SF22. PTHR10628:SF22. 2 hits.
PfamiPF13088. BNR_2. 1 hit.
[Graphical view]
SUPFAMiSSF50939. SSF50939. 2 hits.

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8WWR8-1) [UniParc]FASTAAdd to basket

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.

« Hide

        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
Length:484
Mass (Da):51,572
Last modified:March 7, 2006 - v3
Checksum:i14A878C2A9F18863
GO
Isoform 2 (identifier: Q8WWR8-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MMSSAAFPRWLSM

Show »
Length:496
Mass (Da):52,938
Checksum:i1DE1395862011A36
GO
Isoform 3 (identifier: Q8WWR8-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MMSSAAFPRWLQSM

Note: Gene prediction based on EST data.
Show »
Length:497
Mass (Da):53,066
Checksum:iC933EFAEC7383F69
GO

Sequence cautioni

The sequence AAP34475 differs from that shown. Reason: Frameshift at position 291.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti184R → L in CAC81904 (PubMed:14962670).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_067458301G → R.3 PublicationsCorresponds to variant rs11545301dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0374911M → MMSSAAFPRWLSM in isoform 2. 1 Publication1
Alternative sequenceiVSP_0471231M → MMSSAAFPRWLQSM in isoform 3. Curated1

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.
CCDSiCCDS2553.1. [Q8WWR8-2]
CCDS54441.1. [Q8WWR8-3]
CCDS54442.1. [Q8WWR8-1]
RefSeqiNP_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]
UniGeneiHs.551747.

Genome annotation databases

EnsembliENST00000325935; ENSP00000320318; ENSG00000204099. [Q8WWR8-3]
ENST00000391969; ENSP00000375830; ENSG00000204099. [Q8WWR8-1]
ENST00000404257; ENSP00000385149; ENSG00000204099. [Q8WWR8-2]
ENST00000405370; ENSP00000384804; ENSG00000204099. [Q8WWR8-1]
ENST00000407683; ENSP00000385402; ENSG00000204099. [Q8WWR8-1]
ENST00000616490; ENSP00000482722; ENSG00000277926. [Q8WWR8-2]
ENST00000618866; ENSP00000483726; ENSG00000277926. [Q8WWR8-1]
ENST00000621851; ENSP00000478409; ENSG00000277926. [Q8WWR8-1]
ENST00000626600; ENSP00000485701; ENSG00000277926. [Q8WWR8-3]
ENST00000630923; ENSP00000486602; ENSG00000277926. [Q8WWR8-1]
GeneIDi129807.
KEGGihsa:129807.
UCSCiuc002wcm.4. human. [Q8WWR8-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

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.
CCDSiCCDS2553.1. [Q8WWR8-2]
CCDS54441.1. [Q8WWR8-3]
CCDS54442.1. [Q8WWR8-1]
RefSeqiNP_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]
UniGeneiHs.551747.

3D structure databases

ProteinModelPortaliQ8WWR8.
SMRiQ8WWR8.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi126209. 19 interactors.
IntActiQ8WWR8. 9 interactors.
MINTiMINT-1447950.
STRINGi9606.ENSP00000320318.

Chemistry databases

BindingDBiQ8WWR8.
ChEMBLiCHEMBL4174.
SwissLipidsiSLP:000001400. [Q8WWR8-2]
SLP:000001401. [Q8WWR8-1]

Protein family/group databases

CAZyiGH33. Glycoside Hydrolase Family 33.

PTM databases

iPTMnetiQ8WWR8.
PhosphoSitePlusiQ8WWR8.

Polymorphism and mutation databases

BioMutaiNEU4.
DMDMi90110434.

Proteomic databases

PaxDbiQ8WWR8.
PRIDEiQ8WWR8.

Protocols and materials databases

DNASUi129807.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000325935; ENSP00000320318; ENSG00000204099. [Q8WWR8-3]
ENST00000391969; ENSP00000375830; ENSG00000204099. [Q8WWR8-1]
ENST00000404257; ENSP00000385149; ENSG00000204099. [Q8WWR8-2]
ENST00000405370; ENSP00000384804; ENSG00000204099. [Q8WWR8-1]
ENST00000407683; ENSP00000385402; ENSG00000204099. [Q8WWR8-1]
ENST00000616490; ENSP00000482722; ENSG00000277926. [Q8WWR8-2]
ENST00000618866; ENSP00000483726; ENSG00000277926. [Q8WWR8-1]
ENST00000621851; ENSP00000478409; ENSG00000277926. [Q8WWR8-1]
ENST00000626600; ENSP00000485701; ENSG00000277926. [Q8WWR8-3]
ENST00000630923; ENSP00000486602; ENSG00000277926. [Q8WWR8-1]
GeneIDi129807.
KEGGihsa:129807.
UCSCiuc002wcm.4. human. [Q8WWR8-1]

Organism-specific databases

CTDi129807.
GeneCardsiNEU4.
HGNCiHGNC:21328. NEU4.
HPAiHPA037394.
HPA037395.
MIMi608527. gene.
neXtProtiNX_Q8WWR8.
OpenTargetsiENSG00000204099.
ENSG00000277926.
PharmGKBiPA134917116.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IFVF. Eukaryota.
ENOG410Y74Z. LUCA.
GeneTreeiENSGT00390000011171.
HOGENOMiHOG000233778.
HOVERGENiHBG052608.
InParanoidiQ8WWR8.
KOiK12357.
OMAiHIDCKEC.
OrthoDBiEOG091G08BI.
PhylomeDBiQ8WWR8.
TreeFamiTF331063.

Enzyme and pathway databases

BioCyciZFISH:HS11296-MONOMER.
BRENDAi3.2.1.18. 2681.
ReactomeiR-HSA-1660662. Glycosphingolipid metabolism.
R-HSA-4085001. Sialic acid metabolism.
SABIO-RKQ8WWR8.

Miscellaneous databases

GeneWikiiNEU4.
GenomeRNAii129807.
PROiQ8WWR8.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000204099.
CleanExiHS_NEU4.
ExpressionAtlasiQ8WWR8. baseline and differential.
GenevisibleiQ8WWR8. HS.

Family and domain databases

Gene3Di2.120.10.10. 2 hits.
InterProiIPR026946. Sialidase-4.
IPR026856. Sialidase_fam.
IPR011040. Sialidases.
[Graphical view]
PANTHERiPTHR10628. PTHR10628. 2 hits.
PTHR10628:SF22. PTHR10628:SF22. 2 hits.
PfamiPF13088. BNR_2. 1 hit.
[Graphical view]
SUPFAMiSSF50939. SSF50939. 2 hits.
ProtoNetiSearch...

Entry informationi

Entry nameiNEUR4_HUMAN
AccessioniPrimary (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: November 30, 2016
This is version 131 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Glycosyl hydrolases
    Classification of glycosyl hydrolase families and list of entries
  2. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.