Q99519 · NEUR1_HUMAN
- ProteinSialidase-1
- GeneNEU1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids415 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Catalyzes the removal of sialic acid (N-acetylneuraminic acid) moieties from glycoproteins and glycolipids. To be active, it is strictly dependent on its presence in the multienzyme complex. Appears to have a preference for alpha 2-3 and alpha 2-6 sialyl linkage.
Catalytic activity
pH Dependence
Optimum pH is 4.6.
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 78 | substrate | ||||
Sequence: R | ||||||
Binding site | 97 | substrate | ||||
Sequence: R | ||||||
Active site | 103 | Proton acceptor | ||||
Sequence: D | ||||||
Binding site | 264 | substrate | ||||
Sequence: E | ||||||
Binding site | 280 | substrate | ||||
Sequence: R | ||||||
Binding site | 341 | substrate | ||||
Sequence: R | ||||||
Active site | 370 | Nucleophile | ||||
Sequence: Y | ||||||
Active site | 394 | |||||
Sequence: E |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cell junction | |
Cellular Component | cytoplasm | |
Cellular Component | extracellular exosome | |
Cellular Component | extracellular region | |
Cellular Component | intracellular membrane-bounded organelle | |
Cellular Component | lysosomal lumen | |
Cellular Component | lysosomal membrane | |
Cellular Component | lysosome | |
Cellular Component | membrane | |
Cellular Component | plasma membrane | |
Cellular Component | specific granule lumen | |
Molecular Function | alpha-sialidase activity | |
Molecular Function | exo-alpha-(2->3)-sialidase activity | |
Molecular Function | exo-alpha-(2->6)-sialidase activity | |
Molecular Function | exo-alpha-(2->8)-sialidase activity | |
Molecular Function | exo-alpha-sialidase activity | |
Biological Process | ganglioside catabolic process | |
Biological Process | oligosaccharide catabolic process |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameSialidase-1
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ99519
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Lysosome membrane ; Peripheral membrane protein
Note: Localized not only on the inner side of the lysosomal membrane and in the lysosomal lumen, but also on the plasma membrane and in intracellular vesicles.
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Sialidosis (SIALIDOSIS)
- Note
- DescriptionLysosomal storage disease occurring as two types with various manifestations. Type 1 sialidosis (cherry red spot-myoclonus syndrome or normosomatic type) is late-onset and it is characterized by the formation of cherry red macular spots in childhood, progressive debilitating myoclonus, insiduous visual loss and rarely ataxia. The diagnosis can be confirmed by the screening of the urine for sialyloligosaccharides. Type 2 sialidosis (also known as dysmorphic type) occurs as several variants of increasing severity with earlier age of onset. It is characterized by the presence of abnormal somatic features including coarse facies and dysostosis multiplex, vertebral deformities, intellectual disability, cherry-red spot/myoclonus, sialuria, cytoplasmic vacuolation of peripheral lymphocytes, bone marrow cells and conjunctival epithelial cells.
- See alsoMIM:256550
Natural variants in SIALIDOSIS
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_012207 | 54 | V>M | in SIALIDOSIS; type 1; mild mutation as residual activity is still measurable | |
VAR_012208 | 68 | G>V | in SIALIDOSIS; type 2; less than 10% of activity | |
VAR_017460 | 80 | P>L | in SIALIDOSIS; type 2; no enzyme activity; retained in the endoplasmic reticulum / Golgi or rapidly degraded in the lysosomes; dbSNP:rs104893985 | |
VAR_012209 | 91 | L>R | in SIALIDOSIS; type 2; dbSNP:rs104893972 | |
VAR_012210 | 182 | S>G | in SIALIDOSIS; type 1; normally processed; dbSNP:rs398123392 | |
VAR_012211 | 217 | V>M | in SIALIDOSIS; type 1; partial transport and residual transport activity; dbSNP:rs28940583 | |
VAR_012212 | 219 | G>A | in SIALIDOSIS; type 1; unable to reach the lysosomes; dbSNP:rs754068739 | |
VAR_018076 | 225 | R>P | in SIALIDOSIS; type 2; impaired enzyme folding; dbSNP:rs104893980 | |
VAR_012213 | 227 | G>R | in SIALIDOSIS; type 1 and juvenile type 2; catalytically inactive; retained in pre-lysosomal compartments; dbSNP:rs769765227 | |
VAR_012214 | 231 | L>H | in SIALIDOSIS; type 1; unable to reach the lysosomes; dbSNP:rs762400331 | |
VAR_012215 | 240 | W>R | in SIALIDOSIS; type 2; no enzyme activity; retained in the endoplasmic reticulum / Golgi or rapidly degraded in the lysosomes; dbSNP:rs104893978 | |
VAR_012216 | 243 | G>R | in SIALIDOSIS; type 1; no enzyme activity and no transport to the lysosome; dbSNP:rs104893983 | |
VAR_012217 | 260 | F>Y | in SIALIDOSIS; infantile type 2; catalytically inactive; rapid intralysosomal degradation; dbSNP:rs104893977 | |
VAR_012219 | 270 | L>F | in SIALIDOSIS; type 2; reduction in enzyme activity; rapid intralysosomal degradation | |
VAR_012218 | 270 | L>P | in SIALIDOSIS | |
VAR_012220 | 294 | R>S | in SIALIDOSIS; type 1; mild mutation as residual activity is still measurable; dbSNP:rs190549838 | |
VAR_012221 | 298 | A>V | in SIALIDOSIS; type 2; less than 10% of activity; rapid intralysosomal degradation; impaired enzyme folding; dbSNP:rs104893981 | |
VAR_017461 | 316 | P>S | in SIALIDOSIS; type 1; no enzyme activity; retained in the endoplasmic reticulum / Golgi or rapidly degraded in the lysosomes; dbSNP:rs104893979 | |
VAR_012222 | 328 | G>S | in SIALIDOSIS; type 1; reduction in enzyme activity; dbSNP:rs534846786 | |
VAR_012223 | 335 | P>Q | in SIALIDOSIS; type 2; unable to reach the lysosomes; dbSNP:rs749996046 | |
VAR_018077 | 341 | R>G | in SIALIDOSIS; type 2; affects substrate binding or catalysis; dbSNP:rs751458617 | |
VAR_012224 | 363 | L>P | in SIALIDOSIS; infantile type 2; unable to reach the lysosomes; dbSNP:rs193922915 | |
VAR_012225 | 370 | Y>C | in SIALIDOSIS; infantile type 2; catalytically inactive; dbSNP:rs1310267862 | |
VAR_012226 | 400 | Y>YHY | in SIALIDOSIS; type 1; mild mutation as residual activity is still measurable |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_012207 | 54 | in SIALIDOSIS; type 1; mild mutation as residual activity is still measurable | |||
Sequence: V → M | ||||||
Natural variant | VAR_012208 | 68 | in SIALIDOSIS; type 2; less than 10% of activity | |||
Sequence: G → V | ||||||
Natural variant | VAR_017460 | 80 | in SIALIDOSIS; type 2; no enzyme activity; retained in the endoplasmic reticulum / Golgi or rapidly degraded in the lysosomes; dbSNP:rs104893985 | |||
Sequence: P → L | ||||||
Natural variant | VAR_049203 | 88 | does not affect sialidase activity; dbSNP:rs34712643 | |||
Sequence: G → A | ||||||
Natural variant | VAR_079557 | 90 | does not affect sialidase activity; dbSNP:rs374556080 | |||
Sequence: L → F | ||||||
Natural variant | VAR_012209 | 91 | in SIALIDOSIS; type 2; dbSNP:rs104893972 | |||
Sequence: L → R | ||||||
Natural variant | VAR_079558 | 179 | in dbSNP:rs150302766 | |||
Sequence: V → A | ||||||
Natural variant | VAR_012210 | 182 | in SIALIDOSIS; type 1; normally processed; dbSNP:rs398123392 | |||
Sequence: S → G | ||||||
Natural variant | VAR_079559 | 208 | in dbSNP:rs375104221 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_079560 | 210 | does not affect sialidase activity; dbSNP:rs151177689 | |||
Sequence: P → A | ||||||
Natural variant | VAR_079561 | 217 | significant decrease in sialidase activity; absence of lysosomal localization; mislocalization to the endoplasmic reticulum; dbSNP:rs146850952 | |||
Sequence: V → A | ||||||
Natural variant | VAR_012211 | 217 | in SIALIDOSIS; type 1; partial transport and residual transport activity; dbSNP:rs28940583 | |||
Sequence: V → M | ||||||
Natural variant | VAR_012212 | 219 | in SIALIDOSIS; type 1; unable to reach the lysosomes; dbSNP:rs754068739 | |||
Sequence: G → A | ||||||
Natural variant | VAR_079562 | 222 | does not affect sialidase activity; dbSNP:rs201684013 | |||
Sequence: T → M | ||||||
Natural variant | VAR_018076 | 225 | in SIALIDOSIS; type 2; impaired enzyme folding; dbSNP:rs104893980 | |||
Sequence: R → P | ||||||
Natural variant | VAR_012213 | 227 | in SIALIDOSIS; type 1 and juvenile type 2; catalytically inactive; retained in pre-lysosomal compartments; dbSNP:rs769765227 | |||
Sequence: G → R | ||||||
Natural variant | VAR_012214 | 231 | in SIALIDOSIS; type 1; unable to reach the lysosomes; dbSNP:rs762400331 | |||
Sequence: L → H | ||||||
Natural variant | VAR_079563 | 234 | significant decrease in sialidase activity; absence of lysosomal localization; mislocalization to the endoplasmic reticulum; dbSNP:rs143868999 | |||
Sequence: D → N | ||||||
Natural variant | VAR_012215 | 240 | in SIALIDOSIS; type 2; no enzyme activity; retained in the endoplasmic reticulum / Golgi or rapidly degraded in the lysosomes; dbSNP:rs104893978 | |||
Sequence: W → R | ||||||
Natural variant | VAR_012216 | 243 | in SIALIDOSIS; type 1; no enzyme activity and no transport to the lysosome; dbSNP:rs104893983 | |||
Sequence: G → R | ||||||
Natural variant | VAR_079564 | 248 | in dbSNP:rs373311653 | |||
Sequence: G → S | ||||||
Natural variant | VAR_079565 | 252 | does not affect sialidase activity; dbSNP:rs145177628 | |||
Sequence: G → S | ||||||
Natural variant | VAR_012217 | 260 | in SIALIDOSIS; infantile type 2; catalytically inactive; rapid intralysosomal degradation; dbSNP:rs104893977 | |||
Sequence: F → Y | ||||||
Natural variant | VAR_012219 | 270 | in SIALIDOSIS; type 2; reduction in enzyme activity; rapid intralysosomal degradation | |||
Sequence: L → F | ||||||
Natural variant | VAR_012218 | 270 | in SIALIDOSIS | |||
Sequence: L → P | ||||||
Natural variant | VAR_079566 | 279 | in dbSNP:rs368320390 | |||
Sequence: A → T | ||||||
Natural variant | VAR_012220 | 294 | in SIALIDOSIS; type 1; mild mutation as residual activity is still measurable; dbSNP:rs190549838 | |||
Sequence: R → S | ||||||
Natural variant | VAR_012221 | 298 | in SIALIDOSIS; type 2; less than 10% of activity; rapid intralysosomal degradation; impaired enzyme folding; dbSNP:rs104893981 | |||
Sequence: A → V | ||||||
Natural variant | VAR_017461 | 316 | in SIALIDOSIS; type 1; no enzyme activity; retained in the endoplasmic reticulum / Golgi or rapidly degraded in the lysosomes; dbSNP:rs104893979 | |||
Sequence: P → S | ||||||
Natural variant | VAR_012222 | 328 | in SIALIDOSIS; type 1; reduction in enzyme activity; dbSNP:rs534846786 | |||
Sequence: G → S | ||||||
Natural variant | VAR_012223 | 335 | in SIALIDOSIS; type 2; unable to reach the lysosomes; dbSNP:rs749996046 | |||
Sequence: P → Q | ||||||
Natural variant | VAR_018077 | 341 | in SIALIDOSIS; type 2; affects substrate binding or catalysis; dbSNP:rs751458617 | |||
Sequence: R → G | ||||||
Natural variant | VAR_079567 | 351 | does not affect sialidase activity; dbSNP:rs377573360 | |||
Sequence: S → R | ||||||
Natural variant | VAR_079568 | 357 | in dbSNP:rs139301823 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_012224 | 363 | in SIALIDOSIS; infantile type 2; unable to reach the lysosomes; dbSNP:rs193922915 | |||
Sequence: L → P | ||||||
Natural variant | VAR_012225 | 370 | in SIALIDOSIS; infantile type 2; catalytically inactive; dbSNP:rs1310267862 | |||
Sequence: Y → C | ||||||
Natural variant | VAR_012226 | 400 | in SIALIDOSIS; type 1; mild mutation as residual activity is still measurable | |||
Sequence: Y → YHY | ||||||
Mutagenesis | 412 | Correct sorting to the plasma membrane but no endocytosis and internalization. | ||||
Sequence: Y → A | ||||||
Mutagenesis | 413 | Correct sorting to the plasma membrane but no endocytosis and internalization. | ||||
Sequence: G → A | ||||||
Mutagenesis | 415 | Correct sorting to the plasma membrane but no endocytosis and internalization. | ||||
Sequence: L → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 734 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for signal, chain, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-47 | |||||
Sequence: MTGERPSTALPDRRWGPRILGFWGGCRVWVFAAIFLLLSLAASWSKA | ||||||
Chain | PRO_0000012026 | 48-415 | Sialidase-1 | |||
Sequence: ENDFGLVQPLVTMEQLLWVSGRQIGSVDTFRIPLITATPRGTLLAFAEARKMSSSDEGAKFIALRRSMDQGSTWSPTAFIVNDGDVPDGLNLGAVVSDVETGVVFLFYSLCAHKAGCQVASTMLVWSKDDGVSWSTPRNLSLDIGTEVFAPGPGSGIQKQREPRKGRLIVCGHGTLERDGVFCLLSDDHGASWRYGSGVSGIPYGQPKQENDFNPDECQPYELPDGSVVINARNQNNYHCHCRIVLRSYDACDTLRPRDVTFDPELVDPVVAAGAVVTSSGIVFFSNPAHPEFRVNLTLRWSFSNGTSWRKETVQLWPGPSGYSSLATLEGSMDGEEQAPQLYVLYEKGRNHYTESISVAKISVYGTL | ||||||
Glycosylation | 186 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 343 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 352 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Post-translational modification
N-glycosylated.
Phosphorylation of tyrosine within the internalization signal results in inhibition of sialidase internalization and blockage on the plasma membrane.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Highly expressed in pancreas, followed by skeletal muscle, kidney, placenta, heart, lung and liver. Weakly expressed in brain.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Interacts with cathepsin A (protective protein), beta-galactosidase and N-acetylgalactosamine-6-sulfate sulfatase in a multienzyme complex.
Binary interactions
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for motif, repeat.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Motif | 77-80 | FRIP motif | ||||
Sequence: FRIP | ||||||
Repeat | 112-123 | BNR 1 | ||||
Sequence: RRSMDQGSTWSP | ||||||
Repeat | 172-183 | BNR 2 | ||||
Sequence: VWSKDDGVSWST | ||||||
Repeat | 231-242 | BNR 3 | ||||
Sequence: LLSDDHGASWRY | ||||||
Repeat | 347-358 | BNR 4 | ||||
Sequence: RWSFSNGTSWRK | ||||||
Motif | 412-415 | Internalization signal | ||||
Sequence: YGTL |
Domain
A C-terminal internalization signal (YGTL) appears to allow the targeting of plasma membrane proteins to endosomes.
Sequence similarities
Belongs to the glycosyl hydrolase 33 family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length415
- Mass (Da)45,467
- Last updated1997-05-01 v1
- Checksum360E60A256DEA07F
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
E9PIF4 | E9PIF4_HUMAN | NEU1 | 267 | ||
A0A0G2JKS5 | A0A0G2JKS5_HUMAN | NEU1 | 72 |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF040958 EMBL· GenBank· DDBJ | AAB96774.1 EMBL· GenBank· DDBJ | mRNA | ||
X78687 EMBL· GenBank· DDBJ | CAA55356.1 EMBL· GenBank· DDBJ | mRNA | ||
U84246 EMBL· GenBank· DDBJ | AAD09239.1 EMBL· GenBank· DDBJ | mRNA | ||
AF134726 EMBL· GenBank· DDBJ | AAD21814.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BA000025 EMBL· GenBank· DDBJ | BAB63297.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BT007206 EMBL· GenBank· DDBJ | AAP35870.1 EMBL· GenBank· DDBJ | mRNA | ||
BC000722 EMBL· GenBank· DDBJ | AAH00722.1 EMBL· GenBank· DDBJ | mRNA | ||
BC011900 EMBL· GenBank· DDBJ | AAH11900.1 EMBL· GenBank· DDBJ | mRNA |