Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary extracted from

  • Yardeni, T.; Choekyi, T.; Jacobs, K.; Ciccone, C.; Patzel, K.; Anikster, Y.; Gahl, W.A.; Kurochkina, N.; Huizing, M.
    Identification, tissue distribution, and molecular modeling of novel human isoforms of the key enzyme in sialic acid synthesis, UDP-GlcNAc 2-epimerase/ManNAc kinase (2011), Biochemistry, 50, 8914-8925.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.7.1.60 cloning of isozymes hGNE1-hGNE8, DNA and amino acid sequence determination and analysis, quantitative real-time PCR expression analysis and sequence comparisons Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
3.2.1.183 CMP-Neu5Ac feedback-inhibits the UDPGlcNAc 2-epimerase activity of GNE by binding to its allosteric site Homo sapiens

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
2.7.1.60 cytosol
-
 Homo sapiens 5829
-

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
2.7.1.60 Mg2+ required Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.7.1.60 ATP + N-acyl-D-mannosamine Homo sapiens
-
 ADP + N-acyl-D-mannosamine 6-phosphate
-
 ?
2.7.1.60 additional information Homo sapiens the enzyme is a bifunctional enzyme uridine diphosphate 1-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, i.e. UDP-GlcNAc 2-epimerase/ManNAc kinase or GNE. The N-terminal domain carries out UDP-GlcNAc epimerase function, whereas the C-terminal domain is responsible for ManNAc kinase activity ?
-
 ?
3.2.1.183 UDP-N-acetyl-alpha-D-glucosamine + H2O Homo sapiens
-
 N-acetyl-D-mannosamine + UDP
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.7.1.60 Homo sapiens Q9Y223 eight isozymes hGNE1-hGNE8 from differential splicing
-
3.2.1.183 Homo sapiens Q9Y223 eight isoforms, hGNE1-hGNE8
-

Source Tissue

EC Number Source Tissue Comment Organism Textmining
3.2.1.183 adrenal gland
-
 Homo sapiens
-
3.2.1.183 brain
-
 Homo sapiens
-
3.2.1.183 colon
-
 Homo sapiens
-
3.2.1.183 fibroblast
-
 Homo sapiens
-
3.2.1.183 heart
-
 Homo sapiens
-
3.2.1.183 kidney
-
 Homo sapiens
-
3.2.1.183 leukocyte
-
 Homo sapiens
-
3.2.1.183 liver
-
 Homo sapiens
-
3.2.1.183 lung
-
 Homo sapiens
-
3.2.1.183 additional information quantitative real-time PCR.expression and tissue localization analysis of isozymes GNE1-GNE8, isozymes hGNE1 and hGNE6 is localized ubiquitously in all tissues examined Homo sapiens
-
3.2.1.183 ovary
-
 Homo sapiens
-
3.2.1.183 placenta
-
 Homo sapiens
-
3.2.1.183 prostate
-
 Homo sapiens
-
3.2.1.183 salivary gland
-
 Homo sapiens
-
3.2.1.183 skeletal muscle
-
 Homo sapiens
-
3.2.1.183 small intestine
-
 Homo sapiens
-
3.2.1.183 spleen
-
 Homo sapiens
-
3.2.1.183 testis
-
 Homo sapiens
-
3.2.1.183 thymus
-
 Homo sapiens
-
3.2.1.183 thyroid gland
-
 Homo sapiens
-
3.2.1.183 trachea
-
 Homo sapiens
-
3.2.1.183 uterus
-
 Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.7.1.60 ATP + N-acyl-D-mannosamine
-
 Homo sapiens ADP + N-acyl-D-mannosamine 6-phosphate
-
 ?
2.7.1.60 additional information the enzyme is a bifunctional enzyme uridine diphosphate 1-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, i.e. UDP-GlcNAc 2-epimerase/ManNAc kinase or GNE. The N-terminal domain carries out UDP-GlcNAc epimerase function, whereas the C-terminal domain is responsible for ManNAc kinase activity Homo sapiens ?
-
 ?
3.2.1.183 UDP-N-acetyl-alpha-D-glucosamine + H2O
-
 Homo sapiens N-acetyl-D-mannosamine + UDP
-
 ?

Subunits

EC Number Subunits Comment Organism
2.7.1.60 More the GNE enzyme consists of two enzymatic domains, sequence comparisons, secondary structures, and modeling of isozymes hGNE1-hGNE8, hGNE2 and hGNE7 display a 31-residue N-terminal extension compared to hGNE1. hGNE3 and hGNE8 contain a 55 residue N-terminal deletion, and a 50-residue N-terminal extension compared to hGNE1 Homo sapiens
3.2.1.183 More isozyme sequence comparisons, secondary structures, and structure modeling, overview. Isozymes hGNE2 and hGNE7 display a 31-residue N-terminal extension compared to isozyme hGNE1, isozymes hGNE3 and hGNE8 contain a 53-residue N-terminal deletion and a 50-residue N-terminal extension compared to hGNE1 Homo sapiens

Synonyms

EC Number Synonyms Comment Organism
2.7.1.60 GNE
-
 Homo sapiens
2.7.1.60 UDP-GlcNAc 2-epimerase/ManNAc kinase
-
 Homo sapiens
3.2.1.183 GNE
-
 Homo sapiens
3.2.1.183 UDP-GlcNAc 2-epimerase
-
 Homo sapiens
3.2.1.183 UDP-GlcNAc 2-epimerase/ManNAc kinase
-
 Homo sapiens
3.2.1.183 uridine diphosphate-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase
-
 Homo sapiens

Cofactor

EC Number Cofactor Comment Organism Structure
2.7.1.60 ATP
-
 Homo sapiens

General Information

EC Number General Information Comment Organism
2.7.1.60 malfunction enzyme mutations can cause sialuria and hereditary inclusion body myopathy. Sialuria patients have a heterozygous missense mutation affecting the allosteric site of GNE, leading to loss of feedback inhibition of GNE-epimerase activity by CMP-Neu5Ac, resulting in excessive sialic acid production. HIBM and its allelic Japanese disorder, distal myopathy with rimmed vacuoles, or DMRV, is an autosomal recessive neuromuscular disorder of adult onset, characterized byslowly progressive muscle weakness and atrophy Homo sapiens
2.7.1.60 metabolism UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE) catalyzes the first two committed steps in sialic acid synthesis Homo sapiens
2.7.1.60 additional information epimerase enzymatic activity of isozymes GNE3 and GNE8 is likely absent, since the deleted fragment contains important substrate binding residues in homologous bacterial epimerases. Isozymes hGNE5-hGNE8 have a 53-residue deletion, which is assigned a role in substrate(UDP-GlcNAc) binding Homo sapiens
3.2.1.183 malfunction isozymes hGNE3 and hGNE8 contain a 53-residue N-terminal deletion, epimerase enzymatic activity of isozymes GNE3 and GNE8 is likely absent, because the deleted fragment contains important substrate binding residues in homologous bacterial epimerases. Isozymes hGNE5-hGNE8 have a 53-residue deletion, which was assigned a role in substrate UDP-GlcNAc binding Homo sapiens
3.2.1.183 metabolism the bifunctional enzyme UDP-GlcNAc 2-epimerase/ManNAc kinase, encoded by the GNE gene, catalyzes the first two committed, rate-limiting steps in the biosynthesis of N-acetylneuraminic acid. Two distinct human disorders, sialuria and hereditary inclusion body myopathy, are associated with predominantly missense mutations in GNE Homo sapiens
3.2.1.183 physiological function UDP-GlcNAc 2-epimerase/ManNAc kinase catalyzes the first two committed steps in sialic acid synthesis. Isozyme hGNE1 is the ubiquitously expressed major isoform, while the isozymes hGNE2-hGNE8 isoforms are differentially expressed and may act as tissue-specific regulators of sialylation Homo sapiens