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Identification
HMDB Protein ID HMDBP00332
Secondary Accession Numbers
  • 5568
  • HMDBP09390
Name Bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase
Synonyms
  1. ManAc kinase
  2. N-acetylmannosamine kinase
  3. UDP-GlcNAc-2-epimerase
  4. UDP-GlcNAc-2-epimerase/ManAc kinase
  5. UDP-N-acetylglucosamine 2-epimerase
  6. Uridine diphosphate-N-acetylglucosamine-2-epimerase
  7. SubName: UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase
Gene Name GNE
Protein Type Enzyme
Biological Properties
General Function Involved in ATP binding
Specific 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.
Pathways
  • Amino sugar and nucleotide sugar metabolism
  • Amino Sugar Metabolism
  • G(M2)-Gangliosidosis: Variant B, Tay-sachs disease
  • N-acetylneuraminate biosynthesis
  • Salla Disease/Infantile Sialic Acid Storage Disease
  • Sialuria or French Type Sialuria
  • Sialuria or French Type Sialuria
  • Tay-Sachs Disease
Reactions
Uridine diphosphate-N-acetylglucosamine + Water → N-Acetylmannosamine + Uridine 5'-diphosphate details
Adenosine triphosphate + N-acyl-D-mannosamine → ADP + N-acyl-D-mannosamine 6-phosphate details
Adenosine triphosphate + N-Acetylmannosamine → ADP + N-Acetyl-D-mannosamine 6-phosphate details
GO Classification
Biological Process
lipopolysaccharide biosynthetic process
cell adhesion
N-acetylglucosamine biosynthetic process
N-acetylneuraminate biosynthetic process
N-acetylneuraminate metabolic process
UDP-N-acetylglucosamine metabolic process
Cellular Component
cytosol
cytoplasm
Function
binding
catalytic activity
transferase activity
transferase activity, transferring phosphorus-containing groups
nucleoside binding
purine nucleoside binding
adenyl nucleotide binding
adenyl ribonucleotide binding
atp binding
phosphotransferase activity, alcohol group as acceptor
racemase and epimerase activity
racemase and epimerase activity, acting on carbohydrates and derivatives
udp-n-acetylglucosamine 2-epimerase activity
isomerase activity
Molecular Function
metal ion binding
ATP binding
N-acylmannosamine kinase activity
UDP-N-acetylglucosamine 2-epimerase activity
Process
metabolic process
primary metabolic process
carbohydrate metabolic process
lipopolysaccharide biosynthetic process
udp-n-acetylglucosamine metabolic process
small molecule metabolic process
alcohol metabolic process
monosaccharide metabolic process
amino sugar metabolic process
glucosamine metabolic process
n-acetylglucosamine metabolic process
lipid metabolic process
lipid biosynthetic process
Cellular Location
  1. Cytoplasm
Gene Properties
Chromosome Location 9
Locus 9p13.3
SNPs GNE
Gene Sequence
>2169 bp
ATGGAGAAGAATGGAAATAACCGAAAGCTGCGGGTTTGTGTTGCTACTTGTAACCGTGCA
GATTATTCTAAACTTGCCCCGATCATGTTTGGCATTAAAACCGAACCTGAGTTCTTTGAA
CTTGATGTTGTGGTACTTGGCTCTCACCTGATAGATGACTATGGAAATACATATCGAATG
ATTGAACAAGATGACTTTGACATTAACACCAGGCTACACACAATTGTGAGGGGAGAAGAT
GAGGCAGCCATGGTGGAGTCAGTAGGCCTGGCCCTAGTGAAGCTGCCAGATGTCCTTAAT
CGCCTGAAGCCTGATATCATGATTGTTCATGGAGACAGGTTTGATGCCCTGGCTCTGGCC
ACATCTGCTGCCTTGATGAACATCCGAATCCTTCACATTGAAGGTGGGGAAGTCAGTGGG
ACCATTGATGACTCTATCAGACATGCCATAACAAAACTGGCTCATTATCATGTGTGCTGC
ACCCGCAGTGCAGAGCAGCACCTGATATCCATGTGTGAGGACCATGATCGCATCCTTTTG
GCAGGCTGCCCTTCCTATGACAAACTTCTCTCAGCCAAGAACAAAGACTACATGAGCATC
ATTCGCATGTGGCTAGGTGATGATGTAAAATCTAAAGATTACATTGTTGCACTACAGCAC
CCTGTGACCACTGACATTAAGCATTCCATAAAAATGTTTGAATTAACATTGGATGCACTT
ATCTCATTTAACAAGCGGACCCTAGTCCTGTTTCCAAATATTGACGCAGGGAGCAAAGAG
ATGGTTCGAGTGATGCGGAAGAAGGGCATTGAGCATCATCCCAACTTTCGTGCAGTTAAA
CACGTCCCATTTGACCAGTTTATACAGTTGGTTGCCCATGCTGGCTGTATGATTGGGAAC
AGCAGCTGTGGGGTTCGAGAAGTTGGAGCTTTTGGAACACCTGTGATCAACCTGGGAACA
CGTCAGATTGGAAGAGAAACAGGGGAGAATGTTCTTCATGTCCGGGATGCTGACACCCAA
GACAAAATATTGCAAGCACTGCACCTTCAGTTTGGTAAACAGTACCCTTGTTCAAAGATA
TATGGGGATGGAAATGCTGTTCCAAGGATTTTGAAGTTTCTCAAATCTATCGATCTTCAA
GAGCCACTGCAAAAGAAATTCTGCTTTCCTCCTGTGAAGGAGAATATCTCTCAAGATATT
GACCATATTCTTGAAACTCTAAGTGCCTTGGCCGTTGATCTTGGCGGGACGAACCTCCGA
GTTGCAATAGTCAGCATGAAGGGTGAAATAGTTAAGAAGTATACTCAGTTCAATCCTAAA
ACCTATGAAGAGAGGATTAATTTAATCCTACAGATGTGTGTGGAAGCTGCAGCAGAAGCT
GTAAAACTGAACTGCAGAATTTTGGGAGTAGGCATTTCCACAGGTGGCCGTGTAAATCCT
CGGGAAGGAATTGTGCTGCATTCAACCAAACTGATCCAAGAGTGGAACTCTGTGGACCTT
AGGACCCCCCTTTCTGACACTTTGCATCTCCCTGTGTGGGTAGACAATGATGGCAACTGT
GCTGCCCTGGCGGAAAGGAAATTTGGCCAAGGAAAGGGACTGGAAAACTTTGTTACACTT
ATCACAGGCACAGGAATCGGTGGTGGAATTATCCATCAGCATGAATTGATCCACGGAAGC
TCCTTCTGTGCTGCAGAACTGGGCCACCTTGTTGTGTCTCTGGATGGGCCTGATTGTTCC
TGTGGAAGCCATGGGTGCATTGAAGCATACGCCTCTGGAATGGCCTTGCAGAGGGAGGCA
AAAAAGCTCCATGATGAGGACCTGCTCTTGGTGGAAGGGATGTCAGTGCCAAAAGATGAG
GCTGTGGGTGCGCTCCATCTCATCCAAGCTGCGAAACTTGGCAATGCGAAGGCCCAGAGC
ATCCTAAGAACAGCTGGAACAGCTTTGGGTCTTGGGGTTGTGAACATCCTCCATACCATG
AATCCCTCCCTTGTGATCCTCTCCGGAGTCCTGGCCAGTCACTATATCCACATTGTCAAA
GACGTCATTCGCCAGCAGGCCTTGTCCTCCGTGCAGGACGTGGATGTGGTGGTTTCGGAT
TTGGTTGACCCCGCCCTGCTGGGTGCTGCCAGCATGGTTCTGGACTACACAACACGCAGG
ATCTACTAG
Protein Properties
Number of Residues 722
Molecular Weight 83065.25
Theoretical pI 6.933
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase
MEKNGNNRKLRVCVATCNRADYSKLAPIMFGIKTEPEFFELDVVVLGSHLIDDYGNTYRM
IEQDDFDINTRLHTIVRGEDEAAMVESVGLALVKLPDVLNRLKPDIMIVHGDRFDALALA
TSAALMNIRILHIEGGEVSGTIDDSIRHAITKLAHYHVCCTRSAEQHLISMCEDHDRILL
AGCPSYDKLLSAKNKDYMSIIRMWLGDDVKSKDYIVALQHPVTTDIKHSIKMFELTLDAL
ISFNKRTLVLFPNIDAGSKEMVRVMRKKGIEHHPNFRAVKHVPFDQFIQLVAHAGCMIGN
SSCGVREVGAFGTPVINLGTRQIGRETGENVLHVRDADTQDKILQALHLQFGKQYPCSKI
YGDGNAVPRILKFLKSIDLQEPLQKKFCFPPVKENISQDIDHILETLSALAVDLGGTNLR
VAIVSMKGEIVKKYTQFNPKTYEERINLILQMCVEAAAEAVKLNCRILGVGISTGGRVNP
REGIVLHSTKLIQEWNSVDLRTPLSDTLHLPVWVDNDGNCAALAERKFGQGKGLENFVTL
ITGTGIGGGIIHQHELIHGSSFCAAELGHLVVSLDGPDCSCGSHGCIEAYASGMALQREA
KKLHDEDLLLVEGMSVPKDEAVGALHLIQAAKLGNAKAQSILRTAGTALGLGVVNILHTM
NPSLVILSGVLASHYIHIVKDVIRQQALSSVQDVDVVVSDLVDPALLGAASMVLDYTTRR
IY
GenBank ID Protein 4887658
UniProtKB/Swiss-Prot ID Q9Y223
UniProtKB/Swiss-Prot Entry Name GLCNE_HUMAN
PDB IDs
GenBank Gene ID AF051852
GeneCard ID GNE
GenAtlas ID GNE
HGNC ID HGNC:23657
References
General References
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  5. Seppala R, Lehto VP, Gahl WA: Mutations in the human UDP-N-acetylglucosamine 2-epimerase gene define the disease sialuria and the allosteric site of the enzyme. Am J Hum Genet. 1999 Jun;64(6):1563-9. [PubMed:10330343 ]
  6. Weiss P, Tietze F, Gahl WA, Seppala R, Ashwell G: Identification of the metabolic defect in sialuria. J Biol Chem. 1989 Oct 25;264(30):17635-6. [PubMed:2808337 ]
  7. Keppler OT, Hinderlich S, Langner J, Schwartz-Albiez R, Reutter W, Pawlita M: UDP-GlcNAc 2-epimerase: a regulator of cell surface sialylation. Science. 1999 May 21;284(5418):1372-6. [PubMed:10334995 ]
  8. Ferreira H, Seppala R, Pinto R, Huizing M, Martins E, Braga AC, Gomes L, Krasnewich DM, Sa Miranda MC, Gahl WA: Sialuria in a Portuguese girl: clinical, biochemical, and molecular characteristics. Mol Genet Metab. 1999 Jun;67(2):131-7. [PubMed:10356312 ]
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  11. Arai A, Tanaka K, Ikeuchi T, Igarashi S, Kobayashi H, Asaka T, Date H, Saito M, Tanaka H, Kawasaki S, Uyama E, Mizusawa H, Fukuhara N, Tsuji S: A novel mutation in the GNE gene and a linkage disequilibrium in Japanese pedigrees. Ann Neurol. 2002 Oct;52(4):516-9. [PubMed:12325084 ]
  12. Kayashima T, Matsuo H, Satoh A, Ohta T, Yoshiura K, Matsumoto N, Nakane Y, Niikawa N, Kishino T: Nonaka myopathy is caused by mutations in the UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase gene (GNE). J Hum Genet. 2002;47(2):77-9. [PubMed:11916006 ]
  13. Darvish D, Vahedifar P, Huo Y: Four novel mutations associated with autosomal recessive inclusion body myopathy (MIM: 600737). Mol Genet Metab. 2002 Nov;77(3):252-6. [PubMed:12409274 ]
  14. Tomimitsu H, Ishikawa K, Shimizu J, Ohkoshi N, Kanazawa I, Mizusawa H: Distal myopathy with rimmed vacuoles: novel mutations in the GNE gene. Neurology. 2002 Aug 13;59(3):451-4. [PubMed:12177386 ]
  15. Nishino I, Noguchi S, Murayama K, Driss A, Sugie K, Oya Y, Nagata T, Chida K, Takahashi T, Takusa Y, Ohi T, Nishimiya J, Sunohara N, Ciafaloni E, Kawai M, Aoki M, Nonaka I: Distal myopathy with rimmed vacuoles is allelic to hereditary inclusion body myopathy. Neurology. 2002 Dec 10;59(11):1689-93. [PubMed:12473753 ]
  16. Vasconcelos OM, Raju R, Dalakas MC: GNE mutations in an American family with quadriceps-sparing IBM and lack of mutations in s-IBM. Neurology. 2002 Dec 10;59(11):1776-9. [PubMed:12473769 ]
  17. Broccolini A, Pescatori M, D'Amico A, Sabino A, Silvestri G, Ricci E, Servidei S, Tonali PA, Mirabella M: An Italian family with autosomal recessive inclusion-body myopathy and mutations in the GNE gene. Neurology. 2002 Dec 10;59(11):1808-9. [PubMed:12473780 ]
  18. Eisenberg I, Grabov-Nardini G, Hochner H, Korner M, Sadeh M, Bertorini T, Bushby K, Castellan C, Felice K, Mendell J, Merlini L, Shilling C, Wirguin I, Argov Z, Mitrani-Rosenbaum S: Mutations spectrum of GNE in hereditary inclusion body myopathy sparing the quadriceps. Hum Mutat. 2003 Jan;21(1):99. [PubMed:12497639 ]
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  21. Broccolini A, Ricci E, Cassandrini D, Gliubizzi C, Bruno C, Tonoli E, Silvestri G, Pescatori M, Rodolico C, Sinicropi S, Servidei S, Zara F, Minetti C, Tonali PA, Mirabella M: Novel GNE mutations in Italian families with autosomal recessive hereditary inclusion-body myopathy. Hum Mutat. 2004 Jun;23(6):632. [PubMed:15146476 ]
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  23. Reinke SO, Hinderlich S: Prediction of three different isoforms of the human UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase. FEBS Lett. 2007 Jul 10;581(17):3327-31. Epub 2007 Jun 21. [PubMed:17597614 ]