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Literature summary for 5.1.3.14 extracted from

  • Reinke, S.O.; Lehmer, G.; Hinderlich, S.; Reutter, W.
    Regulation and pathophysiological implications of UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE) as the key enzyme of sialic acid biosynthesis (2009), Biol. Chem., 390, 591-599.
    View publication on PubMed

Protein Variants

Protein Variants Comment Organism
additional information generation of GNE knockout mice by gene targeting, enzyme knockout leads to embryonic lethality, phenotype, overview. Impaired sialylation of glycoconjugates induces cell death, either by the loss of the sialic acid specific masking of cells to prevent proteolytic attack or by the prevention of cell migration and differentiation Mus musculus
additional information sialuria is caused by the loss of feedback control of UDP-GlcNAc 2-epimerase activity due to the mutation of only one of the two arginine residues 263 and 266 Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
CMP-Neu5Ac feedback inhibition Homo sapiens
CMP-Neu5Ac feedback inhibition Mus musculus
CMP-Neu5Ac feedback inhibition Rattus norvegicus
additional information UDP-glycal derivatives as transition state analogues of GNE substrates are synthesized, especially UDP-exo-glycal derivatives, C-glycosidic derivatives of 2-acetamidoglucal, and ketosides as bisubstrate analogues and bis-product analogues, respectively. Derivatives of 1-deoxyiminosugars with and without substitution of the iminogroup in the ring are promising GNE inhibitors, designed as transition-state analogues of the known enzymatic mechanism of UDP-GlcNAc 2-epimerase Homo sapiens
additional information UDP-glycal derivatives as transition state analogues of GNE substrates are synthesized, especially UDP-exo-glycal derivatives, C-glycosidic derivatives of 2-acetamidoglucal, and ketosides as bisubstrate analogues and bis-product analogues, respectively. Derivatives of 1-deoxyiminosugars with and without substitution of the iminogroup in the ring are promising GNE inhibitors, designed as transition-state analogues of the known enzymatic mechanism of UDP-GlcNAc 2-epimerase Mus musculus
additional information UDP-glycal derivatives as transition state analogues of GNE substrates are synthesized, especially UDP-exo-glycal derivatives, C-glycosidic derivatives of 2-acetamidoglucal, and ketosides as bissubstrate analogues and bis-product analogues, respectively. Derivatives of 1-deoxyiminosugars with and without substitution of the iminogroup in the ring are promising GNE inhibitors, designed as transition-state analogues of the known enzymatic mechanism of UDP-GlcNAc 2-epimerase Rattus norvegicus

Localization

Localization Comment Organism GeneOntology No. Textmining
cytosol
-
Mus musculus 5829
-
cytosol
-
Homo sapiens 5829
-
cytosol
-
Rattus norvegicus 5829
-
Golgi membrane associated with the cytoplasmic side Mus musculus 139
-
Golgi membrane associated with the cytoplasmic side Homo sapiens 139
-
Golgi membrane associated with the cytoplasmic side Rattus norvegicus 139
-
nucleus
-
Mus musculus 5634
-
nucleus
-
Homo sapiens 5634
-
nucleus
-
Rattus norvegicus 5634
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
additional information Homo sapiens GNE interacts with proteins involved in the regulation of development, e.g. the transcription factor promyelotic leukemia zinc finger protein, which might play a crucial role in the hereditary inclusion body myopathy. GNE is regulated by a variety of biochemical means, including tetramerization promoted by the substrate UDP-GlcNAc, phosphorylation by protein kinase C and feedback inhibition by CMP-Neu5Ac, which is defect in the human disease sialuria. Multienzyme complexes of GNE with the other enzymes of the sialic acid biosynthesis pathway, either close to the Golgi CMP sialic acid transporter or in particular with the nuclear localized CMP-sialic acid synthetase, are possible ?
-
?
additional information Mus musculus GNE interacts with proteins involved in the regulation of development, e.g. the transcription factor promyelotic leukemia zinc finger protein, which might play a crucial role in the hereditary inclusion body myopathy. GNE is regulated by a variety of biochemical means, including tetramerization promoted by the substrate UDP-GlcNAc, phosphorylation by protein kinase C and feedback inhibition by CMP-Neu5Ac. Multienzyme complexes of GNE with the other enzymes of the sialic acid biosynthesis pathway, either close to the Golgi CMP sialic acid transporter or in particular with the nuclear localized CMP-sialic acid synthetase, are possible ?
-
?
additional information Rattus norvegicus GNE interacts with proteins involved in the regulation of development, e.g. the transcription factor promyelotic leukemia zinc finger protein, which might play a crucial role in the hereditary inclusion body myopathy. GNE is regulated by a variety of biochemical means, including tetramerization promoted by the substrate UDP-GlcNAc, phosphorylation by protein kinase C and feedback inhibition by CMP-Neu5Ac. Multienzyme complexes of GNE with the other enzymes of the sialic acid biosynthesis pathway, either close to the Golgi CMP sialic acid transporter or in particular with the nuclear localized CMP-sialic acid synthetase, are possible ?
-
?
UDP-N-acetyl-D-glucosamine + H2O Mus musculus
-
UDP + N-acetylmannosamine
-
?
UDP-N-acetyl-D-glucosamine + H2O Homo sapiens
-
UDP + N-acetylmannosamine
-
?
UDP-N-acetyl-D-glucosamine + H2O Rattus norvegicus
-
UDP + N-acetylmannosamine
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
three different isozymes, hGNE1, hGNE2, and hGNE3, from the two splice variants including exon A1, The N-terminus of hGNE2 is prolonged by 31 additional amino acids. The lack of exon 2 in the cDNA encoding for hGNE3 leads to loss of the first 55 amino acids of hGNE1
-
Mus musculus
-
-
-
Rattus norvegicus
-
-
-

Posttranslational Modification

Posttranslational Modification Comment Organism
phosphoprotein phosphorylation of GNE by protein kinase C Mus musculus
phosphoprotein phosphorylation of GNE by protein kinase C Homo sapiens
phosphoprotein phosphorylation of GNE by protein kinase C Rattus norvegicus

Source Tissue

Source Tissue Comment Organism Textmining
liver high expression level Mus musculus
-
liver high expression level Homo sapiens
-
liver high expression level Rattus norvegicus
-
additional information GNE2 and GNE3 display tissue-specific expression patterns Homo sapiens
-
placenta high expression level Mus musculus
-
placenta high expression level Homo sapiens
-
placenta high expression level Rattus norvegicus
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information GNE interacts with proteins involved in the regulation of development, e.g. the transcription factor promyelotic leukemia zinc finger protein, which might play a crucial role in the hereditary inclusion body myopathy. GNE is regulated by a variety of biochemical means, including tetramerization promoted by the substrate UDP-GlcNAc, phosphorylation by protein kinase C and feedback inhibition by CMP-Neu5Ac, which is defect in the human disease sialuria. Multienzyme complexes of GNE with the other enzymes of the sialic acid biosynthesis pathway, either close to the Golgi CMP sialic acid transporter or in particular with the nuclear localized CMP-sialic acid synthetase, are possible Homo sapiens ?
-
?
additional information GNE interacts with proteins involved in the regulation of development, e.g. the transcription factor promyelotic leukemia zinc finger protein, which might play a crucial role in the hereditary inclusion body myopathy. GNE is regulated by a variety of biochemical means, including tetramerization promoted by the substrate UDP-GlcNAc, phosphorylation by protein kinase C and feedback inhibition by CMP-Neu5Ac. Multienzyme complexes of GNE with the other enzymes of the sialic acid biosynthesis pathway, either close to the Golgi CMP sialic acid transporter or in particular with the nuclear localized CMP-sialic acid synthetase, are possible Mus musculus ?
-
?
additional information GNE interacts with proteins involved in the regulation of development, e.g. the transcription factor promyelotic leukemia zinc finger protein, which might play a crucial role in the hereditary inclusion body myopathy. GNE is regulated by a variety of biochemical means, including tetramerization promoted by the substrate UDP-GlcNAc, phosphorylation by protein kinase C and feedback inhibition by CMP-Neu5Ac. Multienzyme complexes of GNE with the other enzymes of the sialic acid biosynthesis pathway, either close to the Golgi CMP sialic acid transporter or in particular with the nuclear localized CMP-sialic acid synthetase, are possible Rattus norvegicus ?
-
?
additional information GNE is a bifunctional enzyme with UDP-GlcNAc 2-epimerase and ManNAc kinase activities Mus musculus ?
-
?
additional information GNE is a bifunctional enzyme with UDP-GlcNAc 2-epimerase and ManNAc kinase activities Homo sapiens ?
-
?
additional information GNE is a bifunctional enzyme with UDP-GlcNAc 2-epimerase and ManNAc kinase activities Rattus norvegicus ?
-
?
UDP-N-acetyl-D-glucosamine + H2O
-
Mus musculus UDP + N-acetylmannosamine
-
?
UDP-N-acetyl-D-glucosamine + H2O
-
Homo sapiens UDP + N-acetylmannosamine
-
?
UDP-N-acetyl-D-glucosamine + H2O
-
Rattus norvegicus UDP + N-acetylmannosamine
-
?

Subunits

Subunits Comment Organism
More comparison of the GNE primary structures reveals a high sequence similarity between human and rodent GNE, indicating high evolutionary conservation Mus musculus
More comparison of the GNE primary structures reveals a high sequence similarity between human and rodent GNE, indicating high evolutionary conservation Homo sapiens
More comparison of the GNE primary structures reveals a high sequence similarity between human and rodent GNE, indicating high evolutionary conservation Rattus norvegicus

Synonyms

Synonyms Comment Organism
GNE
-
Mus musculus
GNE
-
Homo sapiens
GNE
-
Rattus norvegicus
UDP-GlcNAc 2-epimerase/ManNAc kinase
-
Mus musculus
UDP-GlcNAc 2-epimerase/ManNAc kinase
-
Homo sapiens
UDP-GlcNAc 2-epimerase/ManNAc kinase
-
Rattus norvegicus
UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase
-
Mus musculus
UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase
-
Homo sapiens
UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase
-
Rattus norvegicus

General Information

General Information Comment Organism
malfunction enzyme deficiency causes the disease sialuria in humans. Hereditary inclusion body myopathy, h-IBM, is also a disease caused by different mutations in the GNE gene, it is an autosomal recessive neuromuscular disorder characterized by adult onset, slowly progressive skeletal muscle weakness, and typical histological features as rimmed vacuoles and filamentous inclusions. Sialuria is caused by the loss of feedback control of UDP-GlcNAc 2-epimerase activity due to the mutation of only one of the two arginine residues 263 and 266. Sialuria leads to massive production of free Neu5Ac, which accumulates in the cytoplasm and results in mental retardation and hepatomegaly Homo sapiens
physiological function the bifunctional enzyme UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, GNE, is the key enzyme for the biosynthesis of N-acetylneuraminic acid, from which all other sialic acids are formed Mus musculus
physiological function the bifunctional enzyme UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, GNE, is the key enzyme for the biosynthesis of N-acetylneuraminic acid, from which all other sialic acids are formed Homo sapiens
physiological function the bifunctional enzyme UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, GNE, is the key enzyme for the biosynthesis of N-acetylneuraminic acid, from which all other sialic acids are formed Rattus norvegicus