GNE
Function
Bifunctional enzyme that possesses both UDP-N-acetylglucosamine 2-epimerase and N-acetylmannosamine kinase activities, and serves as the initiator of the biosynthetic pathway leading to the production of N-acetylneuraminic acid (NeuAc), a critical precursor in the synthesis of sialic acids. By catalyzing this pivotal and rate-limiting step in sialic acid biosynthesis, this enzyme assumes a pivotal role in governing the regulation of cell surface sialylation, playing a role in embryonic angiogenesis (PubMed:10334995, PubMed:11326336, PubMed:14707127, PubMed:16503651, PubMed:2808337, PubMed:38237079). Sialic acids represent a category of negatively charged sugars that reside on the surface of cells as terminal components of glycoconjugates and mediate important functions in various cellular processes, including cell adhesion, signal transduction, and cellular recognition (PubMed:10334995, PubMed:14707127).
Involvement in disease
Sialuria
SIALURIA
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.
None
The disease is caused by variants affecting the gene represented in this entry.
Nonaka myopathy
NM
An autosomal recessive myopathy characterized by early adult onset and progressive distal muscle weakness that preferentially affects the anterior tibial muscles, usually sparing the quadriceps femoris. Some individuals may have involvement of the upper limbs or proximal muscles. Muscle biopsy reveals presence of rimmed vacuoles.
None
The disease is caused by variants affecting the gene represented in this entry.
Thrombocytopenia 12 with or without myopathy
THC12
A form of thrombocytopenia, a hematologic disorder defined by a decrease in the number of platelets in circulating blood, resulting in the potential for increased bleeding and decreased ability for clotting. THC12 is an autosomal recessive form manifesting from infancy or early childhood with bleeding episodes. Clinical features include petechiae, easy bruising, epistaxis, hematomas, menorrhagia, and increased bleeding after trauma or surgery. Rare patients may have thrombocytopenia without bleeding. Some affected individuals have myopathic features, usually apparent in the second or third decades of life.
None
The disease is caused by variants affecting the gene represented in this entry.
Pathway
Amino-sugar metabolism; N-acetylneuraminate biosynthesis.
Post-translational modifications
Phosphorylated. Phosphorylation by PKC activates the UDP-N-acetylglucosamine 2-epimerase activity.
Sequence Similarities
In the N-terminal section; belongs to the UDP-N-acetylglucosamine 2-epimerase family.
In the C-terminal section; belongs to the ROK (NagC/XylR) family.
Tissue Specificity
Highest expression in liver and placenta. Also found in heart, brain, lung, kidney, skeletal muscle and pancreas. Isoform 1 is expressed in heart, brain, kidney, liver, placenta, lung, spleen, pancreas, skeletal muscle and colon. Isoform 2 is expressed mainly in placenta, but also in brain, kidney, liver, lung, pancreas and colon. Isoform 3 is expressed at low level in kidney, liver, placenta and colon.
Cellular localization
- Cytoplasm
- Cytosol
Alternative names
GLCNE, IBM2, GNE, Bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, UDP-GlcNAc-2-epimerase/ManAc kinase