UniProt:Q9Y223 GNE

chain
  • chain:1-722
checksum 4D7D049B06B00077
comment
  • FUNCTION Bifunctional enzyme that possesses both UDP-N-acetylglucosamine 2-epimerase and N-acetylmannosamine kinase activities, and serves as the initiator of the biosynthetic pathway leading to the production of N-acetylneuraminic acid (NeuAc), a critical precursor in the synthesis of sialic acids. By catalyzing this pivotal and rate-limiting step in sialic acid biosynthesis, this enzyme assumes a pivotal role in governing the regulation of cell surface sialylation (PubMed:2808337, PubMed:10334995, PubMed:11326336, PubMed:14707127, PubMed:16503651). Sialic acids represent a category of negatively charged sugars that reside on the surface of cells as terminal components of glycoconjugates and mediate important functions in various cellular processes, including cell adhesion, signal transduction, and cellular recognition (PubMed:10334995, PubMed:14707127).CATALYTIC ACTIVITY H2O + UDP-N-acetyl-alpha-D-glucosamine = H(+) + N-acetyl-D-mannosamine + UDPCATALYTIC ACTIVITY an N-acyl-D-mannosamine + ATP = ADP + an N-acyl-D-mannosamine 6-phosphate + H(+)ACTIVITY REGULATION The UDP-N-acetylglucosamine 2-epimerase activity, in contrast to the N-acetylmannosamine kinase activity, exhibits allosteric regulation by cytidine monophosphate-N-acetylneuraminic acid (CMP-Neu5Ac), the end product of neuraminic acid biosynthesis (PubMed:2808337, PubMed:26980148). Moreover, the activity is contingent upon the oligomeric state of the enzyme. The monomeric form is inactive, while the dimeric form selectively catalyzes the phosphorylation of N-acetylmannosamine. The hexameric form, on the other hand, demonstrates full proficiency in both enzyme activities (By similarity). Furthermore, the UDP-N-acetylglucosamine 2-epimerase activity is increased by PKC-mediated phosphorylation (By similarity).PATHWAY Amino-sugar metabolism; N-acetylneuraminate biosynthesis.SUBUNIT Homodimer (PubMed:19841673, PubMed:22343627). Homotetramer (PubMed:26980148). Homohexamer (PubMed:19841673). The hexameric form exhibits both enzyme activities, whereas the dimeric form only catalyzes the phosphorylation of N-acyl-D-mannosamine (By similarity).INTERACTION 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. Phosphorylation by PKC activates the UDP-N-acetylglucosamine 2-epimerase activity.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.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.SEQUENCE CAUTION Truncated N-terminus.
created [InstanceEdit:143527] Schmidt, EE, 2004-11-12 07:45:10
crossReference
databaseName UniProt
dbId 148003
description
  • recommendedName: fullName evidence="32"Bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase alternativeName: UDP-GlcNAc-2-epimerase/ManAc kinase domain recommendedName: fullName evidence="32"UDP-N-acetylglucosamine 2-epimerase (hydrolyzing) ecNumber evidence="7 19 21 25 26"3.2.1.183 alternativeName: UDP-GlcNAc-2-epimerase alternativeName: Uridine diphosphate-N-acetylglucosamine-2-epimerase /domain domain recommendedName: fullName evidence="32"N-acetylmannosamine kinase ecNumber evidence="19 21"2.7.1.60 alternativeName: ManAc kinase /domain
displayName UniProt:Q9Y223 GNE
geneName
  • GNE
  • GLCNE
  • IBM2
identifier Q9Y223
isSequenceChanged false
keyword
  • 3D-structure
  • Allosteric enzyme
  • Alternative splicing
  • ATP-binding
  • Cytoplasm
  • Disease variant
  • Hydrolase
  • Kinase
  • Metal-binding
  • Multifunctional enzyme
  • Nucleotide-binding
  • Phosphoprotein
  • Reference proteome
  • Transferase
  • Zinc
modified [InstanceEdit:12187927] Wright, Adam, 2024-03-12
name
  • GNE
otherIdentifier
  • 10020
  • 11721769_s_at
  • 11750400_a_at
  • 11751689_a_at
  • 17093920
  • 205042_PM_at
  • 205042_at
  • 3205107
  • 3205109
  • 3205110
  • 3205111
  • 3205112
  • 3205113
  • 3205114
  • 3205120
  • 3205121
  • 3205122
  • 3205124
  • 3205125
  • 3205126
  • 3205127
  • 3205130
  • 3205132
  • 3205133
  • 3205134
  • 3205137
  • 3205138
  • 3205143
  • 36515_at
  • 8161174
  • A_23_P216489
  • GE58366
  • GO:0000166
  • GO:0003824
  • GO:0004553
  • GO:0005515
  • GO:0005524
  • GO:0005737
  • GO:0005829
  • GO:0005975
  • GO:0006045
  • GO:0006047
  • GO:0006054
  • GO:0007155
  • GO:0008152
  • GO:0008761
  • GO:0009384
  • GO:0016301
  • GO:0016310
  • GO:0016740
  • GO:0016787
  • GO:0016853
  • GO:0046835
  • GO:0046872
  • GO:0055086
  • GO:0071704
  • GO:1901135
  • HMNXSV003000929
  • HMNXSV003051746
  • ILMN_1729417
  • PH_hs_0000598
  • TC09001068.hg
  • g6382074_3p_at
physicalEntity
referenceDatabase [ReferenceDatabase:2] UniProt
referenceGene
referenceTranscript
schemaClass ReferenceGeneProduct
secondaryIdentifier
  • GLCNE_HUMAN
  • A6PZH2
  • A6PZH3
  • A7UNU7
  • B2R6E1
  • B7Z372
  • B7Z428
  • D3DRP7
  • F5H499
  • H0YFA7
  • Q0VA94
sequenceLength 722
species [Species:48887] Homo sapiens
url https://purl.uniprot.org/uniprot/Q9Y223
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