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sialidase-1; acetylneuraminyl hydrolase; G9 sialidase; lysosomal sialidase; N-acetyl-alpha-neuraminidase 1 (NEU1, NANH)
Function:
- catalyzes removal of sialic acid (N-acetylneuramic acid) moities from glycoproteins & glycolipids
- activity dependent on its presence in the multienzyme complex
- appears to have a preference for alpha 2-3 & alpha 2-6 sialyl linkage
- hydrolysis of alpha-(2->3)-, alpha-(2->6)-, alpha-(2->8)- glycosidic linkages of terminal sialic acid residues in oligosaccharides, glycoproteins, glycolipids, colominic acid & synthetic substrates
- phosphorylation of Tyr within the internalization signal results in inhibition of sialidase internalization & persistence on the plasma membrane
- interacts with other proteins in a multienzyme complex
- cathepsin A (protective protein)
- beta-galactosidase
- N-acetylgalactosamine-6-sulfate sulfatase
Kinetic parameters:
- pH dependence: optimum pH is 4.6
Structure:
- N-glycosylated
- a C-terminal internalization signal (YGTL) appears to allow targeting of plasma membrane proteins to endosomes
- belongs to the glycosyl hydrolase 33 family
- contains 4 BNR repeats
Compartment:
- lysosome membrane, lumenal side; lysosome lumen
- plasma membrane, cytoplasmic vesicle
Expression:
- expressed in pancreas > skeletal muscle, kidney, placenta, heart, lung & liver
- weakly expressed in brain
Pathology:
- defects in NEU1 are the cause of sialidosis
General
glycoprotein
phosphoprotein
sialidase
Properties
SIZE: entity length = 415 aa
MW = 45 kD
COMPARTMENT: lysosome
cytoplasm
MOTIF: signal sequence {1-47}
FRIP {77-80}
MOTIF: binding site
SITE: 78-78
FOR-BINDING-OF: Substrate
aspartate residue {D103}
BNR {112-123}
BNR {172-183}
N-glycosylation site {N186}
BNR {231-242}
MOTIF: Tyr phosphorylation site {Y242}
Ser phosphorylation site {S244}
Tyr phosphorylation site {Y251}
binding site
SITE: 280-280
FOR-BINDING-OF: Substrate
binding site
SITE: 341-341
FOR-BINDING-OF: Substrate
N-glycosylation site {N343}
BNR {347-358}
MOTIF: N-glycosylation site {N352}
tyrosine residue {Y370}
glutamate residue {E394}
Internalization signal {412-415}
Database Correlations
OMIM correlations
MORBIDMAP 608272
UniProt Q99519
Entrez Gene 4758
Kegg hsa:4758
ENZYME 3.2.1.1
References
- UniProt :accession Q99519
- GeneReviews
http://www.ncbi.nlm.nih.gov/sites/genetests/lab/gene/NEU1
- Wikipedia; Note: neuraminidase entry
http://en.wikipedia.org/wiki/neuraminidase