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MGP004090

UniProt Annotations

Entry Information

Gene Name	glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase
Protein Entry	GLCNE_HUMAN
UniProt ID	Q9Y223
Species	Human

Comments

Comment type	Description
Alternative Products	Event=Alternative splicing; Named isoforms=5; Name=1; Synonyms=GNE1; IsoId=Q9Y223-1; Sequence=Displayed; Name=2; Synonyms=GNE2; IsoId=Q9Y223-2; Sequence=VSP_041027; Name=3; Synonyms=GNE3; IsoId=Q9Y223-3; Sequence=VSP_041028; Name=4; IsoId=Q9Y223-4; Sequence=VSP_043474; Name=5; IsoId=Q9Y223-5; Sequence=VSP_043975, VSP_043976;
Catalytic Activity	ATP + N-acyl-D-mannosamine = ADP + N-acyl-D- mannosamine 6-phosphate.
Catalytic Activity	UDP-N-acetyl-alpha-D-glucosamine + H(2)O = N- acetyl-D-mannosamine + UDP.
Disease	Inclusion body myopathy 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. {ECO:0000269\|PubMed:11528398, ECO:0000269\|PubMed:12409274, ECO:0000269\|PubMed:12473769, ECO:0000269\|PubMed:12473780, ECO:0000269\|PubMed:12497639, ECO:0000269\|PubMed:12811782, ECO:0000269\|PubMed:15146476}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Disease	Nonaka myopathy (NM) [MIM:605820]: 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. {ECO:0000269\|PubMed:11916006, ECO:0000269\|PubMed:12177386, ECO:0000269\|PubMed:12325084, ECO:0000269\|PubMed:12473753, ECO:0000269\|PubMed:12913203}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Disease	Sialuria (SIALURIA) [MIM:269921]: 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. {ECO:0000269\|PubMed:10330343, ECO:0000269\|PubMed:10356312, ECO:0000269\|PubMed:2808337}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Enzyme Regulation	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. {ECO:0000250, ECO:0000269\|PubMed:2808337}.
Function	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. {ECO:0000250, ECO:0000269\|PubMed:10334995}.
Pathway	Amino-sugar metabolism; N-acetylneuraminate biosynthesis.
Ptm	Phosphorylated by PKC. {ECO:0000250}.
Sequence Caution	Sequence=BAH12414.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
Similarity	In the C-terminal section; belongs to the ROK (NagC/XylR) family. {ECO:0000305}.
Similarity	In the N-terminal section; belongs to the UDP-N- acetylglucosamine 2-epimerase family. {ECO:0000305}.
Subcellular Location	Cytoplasm {ECO:0000250}.
Subunit	Homodimer and homohexamer. {ECO:0000269\|PubMed:19841673, ECO:0000269\|PubMed:22343627}.
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. {ECO:0000269\|PubMed:10330343, ECO:0000269\|PubMed:10431835, ECO:0000269\|PubMed:17597614}.