Reactome | GNE phosphorylates ManNAc to ManNAc-6-P

GNE phosphorylates ManNAc to ManNAc-6-P

Stable Identifier

R-HSA-4085028

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

Locations in the PathwayBrowser

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Metabolism of proteins (Homo sapiens)

- Post-translational protein modification (Homo sapiens)
  - Asparagine N-linked glycosylation (Homo sapiens)
    - Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein (Homo sapiens)
      - Synthesis of substrates in N-glycan biosythesis (Homo sapiens)
        
        Sialic acid metabolism (Homo sapiens)
        
        GNE phosphorylates ManNAc to ManNAc-6-P (Homo sapiens)

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UDP N acetylglucosamine 2 epimerase, N acetylmannosamine kinase (GNE) is a bifunctional enzyme in the cytosol that is involved in the first two critical, rate limiting steps of sialic acid (Neu5Ac, N acetylneuraminic acid) biosynthesis. In the second reaction, GNE phosphorylates N-acetylmannosamine (ManNAc) to ManNAc-6-P. There are various disorders associated with defects in the GNE gene. Defects in GNE can cause sialuria (MIM:269921), an inborn error of metabolism characterised by cytoplasmic accumulation and increased urinary excretion of Neu5Ac (Seppala et al. 1999). Mutations causing sialuria are R266W, R266Q and R263L (Seppala et al. 1999). Defects in GNE can also cause hereditary inclusion body myopathy (IBM2; MIM:600737), an autosomal recessive neuromuscular disorder characterised by adult-onset, progressive distal and proximal muscle weakness and wastage. Muscle pathology shows rimmed vacuoles and filamentous inclusions (Eisenberg et al. 2001). The common M712T mutation can cause IBM2, as well as heterozygosity with the mutation M171V (Eisenberg et al. 2001, Argov et al. 2003, Broccolini et al. 2002). Defects in GNE can also cause Nonaka myopathy (NM; MIM:605820), an early adulthood-onset muscular disorder characterised by weakness and wastage of the lower limbs and rimmed vacuoles (Nonaka et al. 1981, Eisenberg et al. 2001). Mutations causing NK include the common V572L, either homozygous or heterozygous with C303V (Tomimitsu et al. 2002, Kayashima et al. 2002) and the heterozygous M712T with A631V indicated that NK and IBM2 are allelic, if not identical, disorders (Tomimitsu et al. 2004).

Literature References

PubMed ID	Title	Journal	Year
7252518	Familial distal myopathy with rimmed vacuole and lamellar (myeloid) body formation Ishiura, S, Nonaka, I, Sunohara, N, Satoyoshi, E	J. Neurol. Sci.	1981
10334995	UDP-GlcNAc 2-epimerase: a regulator of cell surface sialylation Reutter, W, Schwartz-Albiez, R, Langner, J, Pawlita, M, Keppler, OT, Hinderlich, S	Science	1999
11528398	The UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase gene is mutated in recessive hereditary inclusion body myopathy Argov, Z, Grabov-Nardini, G, Mitrani-Rosenbaum, S, Shemesh, M, Olender, T, Chen, M, Lancet, D, Avidan, N, Eisenberg, I, Beckmann, JS, Karpati, G, Barash, M, Potikha, T, Friedmann, A, Bradley, WG, Hochner, H, Baumbach, L, Sadeh, M, Asher, EB, Shmilevich, I	Nat. Genet.	2001
12473780	An Italian family with autosomal recessive inclusion-body myopathy and mutations in the GNE gene D'Amico, A, Pescatori, M, Tonali, PA, Sabino, A, Broccolini, A, Silvestri, G, Ricci, E, Mirabella, M, Servidei, S	Neurology	2002
11916006	Nonaka myopathy is caused by mutations in the UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase gene (GNE) Yoshiura, K, Kishino, T, Satoh, A, Niikawa, N, Nakane, Y, Ohta, T, Kayashima, T, Matsumoto, N, Matsuo, H	J. Hum. Genet.	2002
12743242	Hereditary inclusion body myopathy: the Middle Eastern genetic cluster Eisenberg, I, Wirguin, I, Argov, Z, Grabov-Nardini, G, Mitrani-Rosenbaum, S, Soffer, D, Sadeh, M	Neurology	2003
12177386	Distal myopathy with rimmed vacuoles: novel mutations in the GNE gene Kanazawa, I, Ishikawa, K, Shimizu, J, Ohkoshi, N, Tomimitsu, H, Mizusawa, H	Neurology	2002
10330343	Mutations in the human UDP-N-acetylglucosamine 2-epimerase gene define the disease sialuria and the allosteric site of the enzyme Lehto, VP, Seppala, R, Gahl, WA	Am. J. Hum. Genet.	1999
10431835	Primary structure and expression analysis of human UDP-N-acetyl-glucosamine-2-epimerase/N-acetylmannosamine kinase, the bifunctional enzyme in neuraminic acid biosynthesis Reutter, W, Horstkorte, R, Danker, K, Krause, M, Lucka, L	FEBS Lett.	1999
15136692	Distal myopathy with rimmed vacuoles (DMRV): new GNE mutations and splice variant Kanazawa, I, Ishikawa, K, Shimizu, J, Ohkoshi, N, Tomimitsu, H, Mizusawa, H	Neurology	2004