Alternative name(s):
UDP-GlcNAc-2-epimerase/ManAc kinase
Including the following 2 domains:
UDP-N-acetylglucosamine 2-epimerase
EC=5.1.3.14
Alternative name(s):
UDP-GlcNAc-2-epimerase
Uridine diphosphate-N-acetylglucosamine-2-epimerase
N-acetylmannosamine kinase
EC=2.7.1.60
Alternative name(s):
ManAc kinase
Gene names
Name: GNE
Synonyms: GLCNE
Function
シアル酸前駆体となるNANAの生合成の調節と導入。
Regulates and initiates biosynthesis of N-acetylneuraminic acid (NeuAc), a precursor of sialic acids. Plays an essential role in early development By similarity. Required for normal sialylation in hematopoietic cells. Sialylation is implicated in cell adhesion, signal transduction, tumorigenicity and metastatic behavior of malignant cells. Ref.12
Catalytic activity
UDP-N-acetyl-D-glucosamine = UDP-N-acetyl-D-mannosamine.
ATP + N-acyl-D-mannosamine = ADP + N-acyl-D-mannosamine 6-phosphate.
Enzyme regulation
ノイラミン酸生合成の最終産物であるCMP-Neu5Acによりアロステリックなフィードバック調節を受ける。活性は多量体化に依存する。（単量体は不活性、二量体はManNAcのリン酸化活性のみ、6量体はすべての活性をもつ）
PKCによるリン酸化は酵素活性を増加させる。
Allosterically regulated Probable; feedback inhibited by cytidine monophosphate-N-acetylneuraminic acid (CMP-Neu5Ac), the end product of neuraminic acid biosynthesis. Activity is dependent on oligomerization. The monomer is inactive, whereas the dimer catalyzes only the phosphorylation of N-acetylmannosamine; the hexamer is fully active for both enzyme activities By similarity. Up-regulated after PKC-dependent phosphorylation. Ref.11
Pathway
Amino-sugar metabolism; N-acetylneuraminate biosynthesis.
Subunit structure
Homodimer and homohexamer. Ref.14
Subcellular location
Cytoplasm By similarity.
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. Ref.1 Ref.2 Ref.7
Post-translational modification
Phosphorylated by PKC By similarity.
Involvement in disease
シアル酸尿症は遊離のシアル酸が細胞質に蓄積しグラム単位で尿中に排泄される。UDP-GlcNAc2-エピメラーゼのCMP-Neu5Acによるフィードバック阻害の欠損による。臨床的には成長の遅延、顔貌の変化、肝腫大など。常染色体優性遺伝である。
Defects in GNE are a cause of sialuria (SIALURIA) [MIM:269921]; also known as sialuria French type. 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. Ref.2 Ref.11 Ref.15 Ref.16
封入体筋症タイプ２：成人発症型で緩徐に進行する神経原性の骨格筋障害である。近位筋、遠位筋ともに筋力が低下する。
Defects in GNE are the cause of inclusion body myopathy type 2 (IBM2) [MIM:600737]. Hereditary inclusion body myopathies are a group of neuromuscular disorders characterized by adult onset, slowly progressive distal and proximal weakness and a typical muscle pathology including rimmed vacuoles and filamentous inclusions. IBM2 is an autosomal recessive disorder affecting mainly leg muscles, but with an unusual distribution that spares the quadriceps as also observed in Nonaka myopathy. Ref.17 Ref.20 Ref.23 Ref.24 Ref.25 Ref.26 Ref.28
野中筋症：縁取りのある空胞形成を特徴とする遠位筋の筋症。常染色体劣性遺伝。成人初期に大腿四頭筋など下肢前部の筋肉に発症する。病理的には封入体の周囲に炎症所見を認めない。
Defects in GNE are the cause of Nonaka myopathy (NM) [MIM:605820]; also known as distal myopathy with rimmed vacuoles (DMRV). NM is an autosomal recessive muscular disorder, allelic to inclusion body myopathy 2. It is characterized by weakness of the anterior compartment of the lower limbs with onset in early adulthood, and sparing of the quadriceps muscles. As the inclusion body myopathy, NM is histologically characterized by the presence of numerous rimmed vacuoles without inflammatory changes in muscle specimens. Ref.18 Ref.19 Ref.21 Ref.22 Ref.27
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.
