Center for Bioinformatics
Oxidoreductases | Transferases | Hydrolases | Lyases | Isomerases | Ligases

Basic Information

Enzyme Number

5.1.3.14

Official Name

UDP-N-acetylglucosamine 2-epimerase

Name from literature

n acetylglucosamine epimerase

Pathway from literature

sialic acid biosynthesis

Pathway from KEGG

Carbohydrate Metabolism; Aminosugars metabolism; map00530

Organisms

Human (9606)

Genome localization

9p13.3[10020 ],

Comments

The enzyme hydrolyses the product to UDP and N-acetyl-D-mannosamine.

Rate-limiting Description

"Uridine diphosphate-N-acetylglucosamine 2-epimerase (UDP-GlcNAc 2-epimerase) is an enzyme that catalyzes an early, rate-limiting step in the sialic acid biosynthetic pathway." (10334995)

"The basic defect consists of the very rare occurrence of failed feedback inhibition of a rate-limiting enzyme, in this case uridinediphosphate-N-acetylglucosamine (UDP-GlcNAc) 2-epimerase, by a downstream product, in this case cytidine monophosphate (CMP)-NeuAc." (11326336)

"Sialuria is a rare inborn error of sialic acid (NeuAc) metabolism resulting from failure of CMP-NeuAc to adequately feedback inhibit the rate-limiting enzyme in sialic acid synthesis, UDP N-acetylglucosamine (UDP-GlcNAc) 2-epimerase." (8439453)

Regulatory Information

Regulatory type

Detail

feedback;

"These findings further confirm that homozygous or compound heterozygous mutations of GNE/MNK gene associated with IBM2 are not confined to any single specific region of the enzyme outside its negative feedback regulatory domain located at codons 249-275." (12409274)

key enzyme;

"The bifunctional enzyme UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) is the key enzyme of the biosynthesis of sialic acids, terminal components of glycoconjugates associated with a variety of cellular processes." (17597614)

others;

"UDP-GlcNAc 2-epimerase/ManNAc kinase expression is regulated on the transcriptional level by DNA methylation" (12927803)

phosphorylation;PKC

"Up-regulated after PKC-dependent phosphorylation. (From http://www.expasy.org/uniprot/Q9Y223)" ()

Gene ontology

Gene ontology

GO:0009384 (F) N-acylmannosamine kinase activity [Q9Y223 ];
GO:0006054 (P) N-acetylneuraminate metabolic process [Q9Y223 ];
GO:0004396 (F) hexokinase activity [A6PZH3, A6PZH2 ];
GO:0006096 (P) glycolysis [A6PZH3, A6PZH2 ];
GO:0008761 (F) UDP-N-acetylglucosamine 2-epimerase activity [A6PZH3, Q9Y223, A6PZH2 ];
GO:0006047 (P) UDP-N-acetylglucosamine metabolic process [A6PZH3, Q9Y223, A6PZH2 ];
GO:0005737 (C) cytoplasm [Q9Y223 ];
GO:0009103 (P) lipopolysaccharide biosynthetic process [A6PZH3, Q9Y223, A6PZH2 ];
GO:0005524 (F) ATP binding [A6PZH3, Q9Y223, A6PZH2 ];
GO:0007155 (P) cell adhesion [Q9Y223 ];
GO:0005856 (C) cytoskeleton [Q9Y223 ];

Tissue expression

Tissue From HPRD

Kidney [04825 ];
Heart [04825 ];
Lung [04825 ];
Pancreas [04825 ];
Liver [04825 ];
Placenta [04825 ];
Brain [04825 ];
Muscle [04825 ];

Tissue specificity

Highest expression in liver and placenta. Also found in heart, brain, lung, kidney, skeletal muscle and pancreas [Q9Y223 ];

Subcellular localization

Localization

cytoplasm [Q9Y223 ];

Disease relevance

Disease

Defects in GNE are a cause of sialuria [MIM:269921];
also known as sialuria French type. In sialuria, free sialic acid accumulates in the cytoplasm and gram quantities of neuraminic acid are secreted in the urine. The metabolic defect involves lack of feedback inhibition of UDP-GlcNAc 2-epimerase by CMP-Neu5Ac, resulting in constitutive overproduction of free Neu5Ac. Clinical features include variable degrees of developmental delay, coarse facial features and hepatomegaly. Sialuria inheritance is autosomal dominant [Q9Y223 ];

Defects in GNE are the cause of inclusion body myopathy type 2 (IBM2) [MIM:600737]. Hereditary inclusion body myopathies are a group of neuromuscular disorders characterized by adult onset, slowly progressive distal and proximal weakness and a typical muscle pathology including rimmed vacuoles and filamentous inclusions. IBM2 is an autosomal recessive disorder affecting mainly leg muscles, but with an unusual distribution that spares the quadriceps as also observed in Nonaka myopathy [Q9Y223 ];

Defects in GNE are the cause of Nonaka myopathy (NM) [MIM:605820];
also known as distal myopathy with rimmed vacuoles (DMRV). NM is an autosomal recessive muscular disorder, allelic to inclusion body myopathy 2. It is characterized by weakness of the anterior compartment of the lower limbs with onset in early adulthood, and sparing of the quadriceps muscles. As the inclusion body myopathy, NM is histologically characterized by the presence of numerous rimmed vacuoles without inflammatory changes in muscle specimens [Q9Y223 ];

Links

SwissProt

A6PZH2; A6PZH3; Q9Y223

Entrez Gene

10020

HPRD

04825



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  Last Modified: 2009-03-24  
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