EC Number | Protein Variants | Comment | Organism |
---|---|---|---|
5.1.3.14 | 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 |
5.1.3.14 | 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 |
EC Number | Inhibitors | Comment | Organism | Structure |
---|---|---|---|---|
5.1.3.14 | CMP-Neu5Ac | feedback inhibition | Homo sapiens | |
5.1.3.14 | CMP-Neu5Ac | feedback inhibition | Mus musculus | |
5.1.3.14 | CMP-Neu5Ac | feedback inhibition | Rattus norvegicus | |
5.1.3.14 | 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 | |
5.1.3.14 | 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 | |
5.1.3.14 | 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 |
EC Number | Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|---|
5.1.3.14 | cytosol | - |
Mus musculus | 5829 | - |
5.1.3.14 | cytosol | - |
Homo sapiens | 5829 | - |
5.1.3.14 | cytosol | - |
Rattus norvegicus | 5829 | - |
5.1.3.14 | Golgi membrane | associated with the cytoplasmic side | Mus musculus | 139 | - |
5.1.3.14 | Golgi membrane | associated with the cytoplasmic side | Homo sapiens | 139 | - |
5.1.3.14 | Golgi membrane | associated with the cytoplasmic side | Rattus norvegicus | 139 | - |
5.1.3.14 | nucleus | - |
Mus musculus | 5634 | - |
5.1.3.14 | nucleus | - |
Homo sapiens | 5634 | - |
5.1.3.14 | nucleus | - |
Rattus norvegicus | 5634 | - |
EC Number | Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|---|
5.1.3.14 | 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 | ? | - |
? | |
5.1.3.14 | 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 | ? | - |
? | |
5.1.3.14 | 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 | ? | - |
? | |
5.1.3.14 | UDP-N-acetyl-D-glucosamine + H2O | Mus musculus | - |
UDP + N-acetylmannosamine | - |
? | |
5.1.3.14 | UDP-N-acetyl-D-glucosamine + H2O | Homo sapiens | - |
UDP + N-acetylmannosamine | - |
? | |
5.1.3.14 | UDP-N-acetyl-D-glucosamine + H2O | Rattus norvegicus | - |
UDP + N-acetylmannosamine | - |
? |
EC Number | Organism | UniProt | Comment | Textmining |
---|---|---|---|---|
5.1.3.14 | 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 | - |
5.1.3.14 | Mus musculus | - |
- |
- |
5.1.3.14 | Rattus norvegicus | - |
- |
- |
EC Number | Posttranslational Modification | Comment | Organism |
---|---|---|---|
5.1.3.14 | phosphoprotein | phosphorylation of GNE by protein kinase C | Mus musculus |
5.1.3.14 | phosphoprotein | phosphorylation of GNE by protein kinase C | Homo sapiens |
5.1.3.14 | phosphoprotein | phosphorylation of GNE by protein kinase C | Rattus norvegicus |
EC Number | Source Tissue | Comment | Organism | Textmining |
---|---|---|---|---|
5.1.3.14 | liver | high expression level | Mus musculus | - |
5.1.3.14 | liver | high expression level | Homo sapiens | - |
5.1.3.14 | liver | high expression level | Rattus norvegicus | - |
5.1.3.14 | additional information | GNE2 and GNE3 display tissue-specific expression patterns | Homo sapiens | - |
5.1.3.14 | placenta | high expression level | Mus musculus | - |
5.1.3.14 | placenta | high expression level | Homo sapiens | - |
5.1.3.14 | placenta | high expression level | Rattus norvegicus | - |
EC Number | Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|---|
5.1.3.14 | 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 | ? | - |
? | |
5.1.3.14 | 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 | ? | - |
? | |
5.1.3.14 | 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 | ? | - |
? | |
5.1.3.14 | additional information | GNE is a bifunctional enzyme with UDP-GlcNAc 2-epimerase and ManNAc kinase activities | Mus musculus | ? | - |
? | |
5.1.3.14 | additional information | GNE is a bifunctional enzyme with UDP-GlcNAc 2-epimerase and ManNAc kinase activities | Homo sapiens | ? | - |
? | |
5.1.3.14 | additional information | GNE is a bifunctional enzyme with UDP-GlcNAc 2-epimerase and ManNAc kinase activities | Rattus norvegicus | ? | - |
? | |
5.1.3.14 | UDP-N-acetyl-D-glucosamine + H2O | - |
Mus musculus | UDP + N-acetylmannosamine | - |
? | |
5.1.3.14 | UDP-N-acetyl-D-glucosamine + H2O | - |
Homo sapiens | UDP + N-acetylmannosamine | - |
? | |
5.1.3.14 | UDP-N-acetyl-D-glucosamine + H2O | - |
Rattus norvegicus | UDP + N-acetylmannosamine | - |
? |
EC Number | Subunits | Comment | Organism |
---|---|---|---|
5.1.3.14 | More | comparison of the GNE primary structures reveals a high sequence similarity between human and rodent GNE, indicating high evolutionary conservation | Mus musculus |
5.1.3.14 | More | comparison of the GNE primary structures reveals a high sequence similarity between human and rodent GNE, indicating high evolutionary conservation | Homo sapiens |
5.1.3.14 | More | comparison of the GNE primary structures reveals a high sequence similarity between human and rodent GNE, indicating high evolutionary conservation | Rattus norvegicus |
EC Number | Synonyms | Comment | Organism |
---|---|---|---|
5.1.3.14 | GNE | - |
Mus musculus |
5.1.3.14 | GNE | - |
Homo sapiens |
5.1.3.14 | GNE | - |
Rattus norvegicus |
5.1.3.14 | UDP-GlcNAc 2-epimerase/ManNAc kinase | - |
Mus musculus |
5.1.3.14 | UDP-GlcNAc 2-epimerase/ManNAc kinase | - |
Homo sapiens |
5.1.3.14 | UDP-GlcNAc 2-epimerase/ManNAc kinase | - |
Rattus norvegicus |
5.1.3.14 | UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase | - |
Mus musculus |
5.1.3.14 | UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase | - |
Homo sapiens |
5.1.3.14 | UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase | - |
Rattus norvegicus |
EC Number | General Information | Comment | Organism |
---|---|---|---|
5.1.3.14 | 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 |
5.1.3.14 | 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 |
5.1.3.14 | 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 |
5.1.3.14 | 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 |