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Literature summary for 5.1.3.14 extracted from

  • Kurochkina, N.; Yardeni, T.; Huizing, M.
    Molecular modeling of the bifunctional enzyme UDP-GlcNAc 2-epimerase/ManNAc kinase and predictions of structural effects of mutations associated with HIBM and sialuria (2010), Glycobiology, 20, 322-337.
    View publication on PubMedView publication on EuropePMC

Protein Variants

Protein Variants Comment Organism
C13S a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme Homo sapiens
C303V a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme Homo sapiens
C303X a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme Homo sapiens
D176V a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme Homo sapiens
D225N a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme Homo sapiens
D378Y a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme Homo sapiens
G135V a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme Homo sapiens
G206S a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme Homo sapiens
G89R a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme Homo sapiens
H132Q a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme Homo sapiens
I200F a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme Homo sapiens
I241S a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme Homo sapiens
L379H a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme Homo sapiens
M171V a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme Homo sapiens
M29T a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme Homo sapiens
M712T the Persian-Jewish HIBM founder mutation is located at the interface alpha4alpha10 of GNE and likely affects GlcNAc, Mg2+, and ATP binding Homo sapiens
additional information mutant genotyping, overview. Modeling of effects of GNE/MNK missense mutations associated with HIBM or sialuria on helix arrangement, substrate binding, and enzyme action, overview. All reported mutations are associated with the active sites or secondary structure interfaces of GNE/MNK Homo sapiens
P27S a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme Homo sapiens
P283S a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme Homo sapiens
P36L a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme Homo sapiens
R11W a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme Homo sapiens
R129Q a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme Homo sapiens
R162C a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme Homo sapiens
R177C a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme Homo sapiens
R202L a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme Homo sapiens
R246Q a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme Homo sapiens
R246W a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme Homo sapiens
R263L a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme Homo sapiens
R266Q a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme Homo sapiens
R266W a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme Homo sapiens
R277C a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme Homo sapiens
R306Q a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme Homo sapiens
R335W a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme Homo sapiens
V216A a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme Homo sapiens
V331A a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme Homo sapiens
V367I a naturally occuirng missense mutation the epimerase part of the bifunctional enzyme Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
CMP-sialic acid GNE/MNK is feedback inhibited by binding of the downstream product, CMP-sialic acid, in its allosteric site. The allosteric regulation by CMP-sialic acid involves residues D255, E260, R263, R266, K268, and N275 Homo sapiens

Natural Substrates/ Products (Substrates)

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

Organism

Organism UniProt Comment Textmining
Homo sapiens Q9Y223 gene GNE
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information GNE is a bifunctional enzyme with UDP-GlcNAc 2-epimerase and ManNAc kinase activities Homo sapiens ?
-
?
UDP-N-acetyl-D-glucosamine + H2O
-
Homo sapiens UDP + N-acetylmannosamine
-
?
UDP-N-acetyl-D-glucosamine + H2O epimerase active site amino acid residues D21, G111, H132, G136 and D144 are required for stabilization of the active site structure, residues R19, S301 and E307 are involved in binding of the UDP portion of the substrate. Amino acid residues K24, P27, M29, D112, E134, D143, D144, R147, S302 and R113 are located in vicinity of the active site, while residues G182 and D187 are part of the active site hinge region. The possible general catalyst is residue H220, and residues H45 and H132 are required for 2-epimerase activity Homo sapiens UDP + N-acetylmannosamine
-
?

Subunits

Subunits Comment Organism
More modeling of the active sites of human GNE/MNK using vailable structural data of GNE/MNK homologues, overview Homo sapiens

Synonyms

Synonyms Comment Organism
GNE
-
Homo sapiens
GNE/MNK
-
Homo sapiens
UDP-GlcNAc 2-epimerase/ManNAc kinase
-
Homo sapiens

General Information

General Information Comment Organism
malfunction GNE mutations can result in two human disorders, hereditary inclusion body myopathy, HIBM, and sialuria Homo sapiens
metabolism GNE catalyzes the first two committed, rate-limiting steps in the biosynthesis of N-acetylneuraminic acid, i.e. sialic acid Homo sapiens