Literature summary for 3.2.1.183 extracted from

Grover, S.; Arya, R.
Role of UDP-N-acetylglucosamine2-epimerase/N-acetylmannosamine kinase (GNE) in beta-integrin-mediated cell adhesion (2014), Mol. Neurobiol., 50, 257-273 .

Search for more literature for 3.2.1.183

Cloned(Commentary)

Cloned (Comment)	Organism
gene gne, overexpresion of wild-type and mutant enzymes in HEK-293 cells, the endogenous GNE is knocked down in HEK-293 cells using GNE-specific shRNA	Homo sapiens

Protein Variants

Protein Variants	Comment	Organism
D176V	naturally occuring mutation in hereditary inclusion body myopathy (GNE myopathy) patients, phenotype, detailed overview. The mutant enzyme shows 85% reduced activity of the epimerase compared to the wild-type enzyme	Homo sapiens
additional information	endogenous GNE is knocked down from normal HEK cells using shRNA, sialic acid quantitation in GNE overexpressed and knockdown cells, overview. Presence of r-wt-GNE and r-V572L-GNE proteins in nucleus while r-D176V-GNE primarily in the cytoplasm suggesting that mutation in the epimerase domain might prevent nuclear localization of GNE. Activation of endoplasmic reticulum stress response due to accumulation of misfolded mutated GNE protein. Hyposialylation caused due to mutation in GNE is affecting the membrane localization of beta1-integrin	Homo sapiens
V572L	naturally occuring mutation in hereditary inclusion body myopathy (GNE myopathy) patients, phenotype, detailed overview. The mutant enzyme shows 44% reduced activity of the epimerase compared to the wild-type enzyme	Homo sapiens

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
cytosol	-	Homo sapiens	5829	-
Golgi membrane	cytoplasmic side of the Golgi membrane	Homo sapiens	139	-
nucleus	-	Homo sapiens	5634	-

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
UDP-N-acetyl-alpha-D-glucosamine + H2O	Homo sapiens	-	N-acetyl-D-mannosamine + UDP	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	Q9Y223	-	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
neuron	-	Homo sapiens	-
skeletal muscle	-	Homo sapiens	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
UDP-N-acetyl-alpha-D-glucosamine + H2O	-	Homo sapiens	N-acetyl-D-mannosamine + UDP	-	?

Subunits

Subunits	Comment	Organism
More	in the dimeric state GNE possess only kinase activity, in the hexameric state it displays both the epimerase and kinase activities while no activity is observed when GNE is present as a monomer	Homo sapiens
oligomer	x * 79000, SDS-PAGE	Homo sapiens

Synonyms

Synonyms	Comment	Organism
GNE	-	Homo sapiens
UDP-N-acetylglucosamine2-epimerase/N-acetylmannosamine kinase	-	Homo sapiens

General Information

General Information	Comment	Organism
malfunction	hereditary inclusion body myopathy (GNE myopathy) is a neuromuscular disorder due to mutation in key sialic acid biosynthetic enzyme, GNE. The subcellular distribution of recombinant GNE and its mutant shows differential localization in the cell. The enzyme mutation leads to hyposialylation of cell membrane receptor, beta1-integrin. Hyposialylated beta1-integrin localized to internal vesicles that is restored upon supplementation with sialic acid. Fibronectin stimulation causes migration of hyposialylated beta1-integrin to the cell membrane and colocalization with focal adhesion kinase (FAK) leading to increased focal adhesion formation. This further activates FAK and Src, downstream signaling molecules and leads to increased cell adhesion. The mutation in GNE affects beta1-integrin-mediated cell adhesion process in GNE mutant cells. Activation of endoplasmic reticulum stress response due to accumulation of misfolded mutated GNE protein	Homo sapiens
metabolism	bifunctional UDP-N-acetylglucosamine2-epimerase/N-acetylmannosamine kinase, GNE, is key sialic acid biosynthetic enzyme	Homo sapiens
additional information	in the dimeric state GNE possess only kinase activity, in the hexameric state it displays both the epimerase and kinase activities while no activity is observed when GNE is present as a monomer	Homo sapiens
physiological function	biosynthesis of sialic acid is regulated by a 79-kDa bifunctional enzyme UDP-N-acetylglucosamine2-epimerase/N-acetylmannosamine kinase (GNE), consisting of N-terminal epimerase and C-terminal kinase domain. The epimerase domain converts UDP-GlcNAc to ManNAc and kinase domain phosphorylates ManNAc to ManNAc phosphate	Homo sapiens

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Release 2023.1 (January 2023)