★GNE

The protein encoded by this gene is a bifunctional enzyme that initiates and regulates the biosynthesis of N-acetylneuraminic acid (NeuAc), a precursor of sialic acids. It is a rate-limiting enzyme in the sialic acid biosynthetic pathway. Sialic acid modification of cell surface molecules is crucial for their function in many biologic processes, including cell adhesion and signal transduction. Differential sialylation of cell surface molecules is also implicated in the tumorigenicity and metastatic behavior of malignant cells. Mutations in this gene are associated with sialuria, autosomal recessive inclusion body myopathy, and Nonaka myopathy. Alternative splicing of this gene results in transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
Diseases associated with GNE include Nonaka Myopathy and Sialuria. Among its related pathways are Diseases of glycosylation and Synthesis of substrates in N-glycan biosythesis. Gene Ontology (GO) annotations related to this gene include hydrolase activity, hydrolyzing O-glycosyl compounds and UDP-N-acetylglucosamine 2-epimerase activity.
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, 11326336, 14707127, 16503651, 2808337, 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, 14707127).
The UDP-N-acetylglucosamine 2-epimerase activity, in contrast to the N-acetylmannosamine kinase activity, exhibits allosteric regulation by cytidine monophosphate-N-acetylneuraminic acid (CMP-Neu5Ac), the end product of neuraminic acid biosynthesis (PubMed:26980148, 2808337).
Moreover, the activity is contingent upon the oligomeric state of the enzyme.
The monomeric form is inactive, while the dimeric form selectively catalyzes the phosphorylation of N-acetylmannosamine.
The hexameric form, on the other hand, demonstrates full proficiency in both enzyme activities (By similarity).
Furthermore, the UDP-N-acetylglucosamine 2-epimerase activity is increased by PKC-mediated phosphorylation (By similarity).
neutrophil migration
Cytoplasm, cytosol {ECO:0000250 UniProtKB:O35826}5
Quaternary structure:
Homodimer (PubMed:19841673, 22343627).
Homotetramer (PubMed:26980148).
Homohexamer (PubMed:19841673).
The hexameric form exhibits both enzyme activities, whereas the dimeric form only catalyzes the phosphorylation of N-acyl-D-mannosamine (By similarity).