Human Gene GNE (ENST00000539208.5) from GENCODE V44
Description: Homo sapiens glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase (GNE), transcript variant 5, mRNA. (from RefSeq NM_001190384) RefSeq Summary (NM_001190384): The protein encoded by this gene is a bifunctional enzyme that initiates and regulates the biosynthesis of N-acetylneuraminic acid (NeuAc), a precursor of sialic acids. It is a rate-limiting enzyme in the sialic acid biosynthetic pathway. Sialic acid modification of cell surface molecules is crucial for their function in many biologic processes, including cell adhesion and signal transduction. Differential sialylation of cell surface molecules is also implicated in the tumorigenicity and metastatic behavior of malignant cells. Mutations in this gene are associated with sialuria, autosomal recessive inclusion body myopathy, and Nonaka myopathy. Alternative splicing of this gene results in transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]. Sequence Note: This RefSeq record was created from transcript and genomic sequence data to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on transcript alignments. Gencode Transcript: ENST00000539208.5 Gencode Gene: ENSG00000159921.20 Transcript (Including UTRs) Position: hg38 chr9:36,217,152-36,258,445 Size: 41,294 Total Exon Count: 10 Strand: - Coding Region Position: hg38 chr9:36,217,365-36,246,469 Size: 29,105 Coding Exon Count: 9
ID:GLCNE_HUMAN DESCRIPTION: RecName: Full=Bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase; AltName: Full=UDP-GlcNAc-2-epimerase/ManAc kinase; Includes: RecName: Full=UDP-N-acetylglucosamine 2-epimerase; EC=5.1.3.14; AltName: Full=UDP-GlcNAc-2-epimerase; AltName: Full=Uridine diphosphate-N-acetylglucosamine-2-epimerase; Includes: RecName: Full=N-acetylmannosamine kinase; EC=2.7.1.60; AltName: Full=ManAc kinase; 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. CATALYTIC ACTIVITY: UDP-N-acetyl-D-glucosamine = UDP-N-acetyl-D- mannosamine. CATALYTIC ACTIVITY: ATP + N-acyl-D-mannosamine = ADP + N-acyl-D- mannosamine 6-phosphate. 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. PATHWAY: Amino-sugar metabolism; N-acetylneuraminate biosynthesis. SUBUNIT: Homodimer and homohexamer. 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. PTM: Phosphorylated by PKC (By similarity). DISEASE: 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. DISEASE: 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. DISEASE: 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. SIMILARITY: In the N-terminal section; belongs to the UDP-N- acetylglucosamine 2-epimerase family. SIMILARITY: In the C-terminal section; belongs to the ROK (NagC/XylR) family. WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/GNE";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9Y223
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
LP895623 - Sequence 487 from Patent EP3253886. AJ238764 - Homo sapiens mRNA for UDP-N-acetylglucosamine-2-epimerase / N-acetylmannosamine kinase. AY531126 - Homo sapiens isolate Y7303-49 UDP-N-acetylglucosamine-2-epimerase / N-acetylmannosamine kinase (GNE) mRNA, complete cds. AY531127 - Homo sapiens isolate Y9103-50 UDP-N-acetylglucosamine-2-epimerase / N-acetylmannosamine kinase (GNE) mRNA, complete cds. AY531128 - Homo sapiens isolate W7803-30 UDP-N-acetylglucosamine-2-epimerase / N-acetylmannosamine kinase (GNE) mRNA, complete cds. AK299488 - Homo sapiens cDNA FLJ58375 complete cds, moderately similar to Bifunctional UDP-N-acetylglucosamine2-epimerase/N-acetylmannosamine kinase. AK296687 - Homo sapiens cDNA FLJ52319 complete cds, highly similar to Bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase. AK295562 - Homo sapiens cDNA FLJ51479 complete cds, highly similar to Bifunctional UDP-N-acetylglucosamine2-epimerase/N-acetylmannosamine kinase. EU093084 - Homo sapiens isolate GNE-1 mutant UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase mRNA, complete cds, alternatively spliced. BC121179 - Homo sapiens glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase, mRNA (cDNA clone MGC:150583 IMAGE:40122902), complete cds. JD301018 - Sequence 282042 from Patent EP1572962. AF051852 - Homo sapiens UDP-N-acetylglucosamine-2-epimerase mRNA, complete cds. JD236399 - Sequence 217423 from Patent EP1572962. JD181071 - Sequence 162095 from Patent EP1572962. JD173213 - Sequence 154237 from Patent EP1572962. JD240546 - Sequence 221570 from Patent EP1572962. AF155663 - Homo sapiens UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase mRNA, complete cds. AM697709 - Homo sapiens mRNA for UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE gene), GNE3 isoform. AM697708 - Homo sapiens mRNA for UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE gene), putative GNE1 and GNE2 isoforms. AK312539 - Homo sapiens cDNA, FLJ92908, Homo sapiensUDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase(GNE), mRNA. KJ892899 - Synthetic construct Homo sapiens clone ccsbBroadEn_02293 GNE gene, encodes complete protein. KR711940 - Synthetic construct Homo sapiens clone CCSBHm_00032504 GNE (GNE) mRNA, encodes complete protein. KR711941 - Synthetic construct Homo sapiens clone CCSBHm_00032513 GNE (GNE) mRNA, encodes complete protein. KR711942 - Synthetic construct Homo sapiens clone CCSBHm_00032524 GNE (GNE) mRNA, encodes complete protein. KR711943 - Synthetic construct Homo sapiens clone CCSBHm_00032537 GNE (GNE) mRNA, encodes complete protein. DQ591819 - Homo sapiens piRNA piR-58931, complete sequence.
Biochemical and Signaling Pathways
KEGG - Kyoto Encyclopedia of Genes and Genomes hsa00520 - Amino sugar and nucleotide sugar metabolism hsa01100 - Metabolic pathways
Reactome (by CSHL, EBI, and GO)
Protein Q9Y223 (Reactome details) participates in the following event(s):
R-HSA-4085028 GNE phosphorylates ManNAc to ManNAc-6-P R-HSA-4085021 GNE hydrolyzes/epimerises UDP-GlcNAc to ManNAc and UDP R-HSA-4085001 Sialic acid metabolism R-HSA-446219 Synthesis of substrates in N-glycan biosythesis R-HSA-446193 Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein R-HSA-446203 Asparagine N-linked glycosylation R-HSA-597592 Post-translational protein modification R-HSA-392499 Metabolism of proteins