Q91WG8 · GLCNE_MOUSE
- ProteinBifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase
- GeneGne
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids722 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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, playing a role in embryonic angiogenesis (PubMed:11929971, PubMed:38237079).
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 (By similarity).
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 (By similarity).
Catalytic activity
- H2O + UDP-N-acetyl-alpha-D-glucosamine = aldehydo-N-acetyl-D-mannosamine + H+ + UDPThis reaction proceeds in the forward direction.
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 (By similarity).
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 (PubMed:10745088).
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 (PubMed:10745088).
Pathway
Amino-sugar metabolism; N-acetylneuraminate biosynthesis.
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 19 | UDP (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 23 | UDP (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 113 | UDP (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 220 | UDP (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 253 | UDP (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 259 | CMP-N-acetyl-beta-neuraminate (UniProtKB | ChEBI); allosteric inhibitor | ||||
Sequence: K | ||||||
Binding site | 271 | CMP-N-acetyl-beta-neuraminate (UniProtKB | ChEBI); allosteric inhibitor | ||||
Sequence: E | ||||||
Binding site | 280 | CMP-N-acetyl-beta-neuraminate (UniProtKB | ChEBI); allosteric inhibitor | ||||
Sequence: K | ||||||
Binding site | 281 | CMP-N-acetyl-beta-neuraminate (UniProtKB | ChEBI); allosteric inhibitor | ||||
Sequence: H | ||||||
Binding site | 282 | UDP (UniProtKB | ChEBI) | ||||
Sequence: V | ||||||
Binding site | 301 | UDP (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 302 | UDP (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 307 | UDP (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 321 | UDP (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 413 | Mg2+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 416 | an N-acyl-D-mannosamine 6-phosphate (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 417 | ADP (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 418 | ADP (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 420 | ADP (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 476 | an N-acyl-D-mannosamine (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 476 | an N-acyl-D-mannosamine 6-phosphate (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 477 | an N-acyl-D-mannosamine (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 477 | an N-acyl-D-mannosamine 6-phosphate (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 489 | an N-acyl-D-mannosamine (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 489 | an N-acyl-D-mannosamine 6-phosphate (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 516 | an N-acyl-D-mannosamine (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 516 | an N-acyl-D-mannosamine 6-phosphate (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Active site | 517 | |||||
Sequence: D | ||||||
Binding site | 517 | an N-acyl-D-mannosamine (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 517 | an N-acyl-D-mannosamine 6-phosphate (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 545 | an N-acyl-D-mannosamine 6-phosphate (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 566 | an N-acyl-D-mannosamine (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 569 | an N-acyl-D-mannosamine (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 569 | an N-acyl-D-mannosamine 6-phosphate (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 569 | Zn2+ (UniProtKB | ChEBI); structural | ||||
Sequence: H | ||||||
Binding site | 579 | Zn2+ (UniProtKB | ChEBI); structural | ||||
Sequence: C | ||||||
Binding site | 581 | Zn2+ (UniProtKB | ChEBI); structural | ||||
Sequence: C | ||||||
Binding site | 586 | Zn2+ (UniProtKB | ChEBI); structural | ||||
Sequence: C | ||||||
Binding site | 588 | an N-acyl-D-mannosamine (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 588 | an N-acyl-D-mannosamine 6-phosphate (UniProtKB | ChEBI) | ||||
Sequence: E |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytosol | |
Molecular Function | ATP binding | |
Molecular Function | catalytic activity | |
Molecular Function | hydrolase activity, hydrolyzing O-glycosyl compounds | |
Molecular Function | metal ion binding | |
Molecular Function | N-acylmannosamine kinase activity | |
Molecular Function | UDP-N-acetylglucosamine 2-epimerase activity | |
Biological Process | N-acetylglucosamine biosynthetic process | |
Biological Process | N-acetylneuraminate biosynthetic process | |
Biological Process | N-acetylneuraminate metabolic process | |
Biological Process | UDP-N-acetylglucosamine metabolic process |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameBifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase
- Alternative names
Including 2 domains:
- Recommended nameUDP-N-acetylglucosamine 2-epimerase (hydrolyzing)
- EC number
- Alternative names
- Recommended nameN-acetylmannosamine kinase
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ91WG8
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Phenotypes & Variants
Disruption phenotype
Knockout of the gene is embryonic lethal.
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 563 | Loss-of-function mutant resulting in impaired sialic acid biosynthesis. | ||||
Sequence: C → Y | ||||||
Mutagenesis | 704 | Homozygous embryos exhibit cerebrospinal hemorrhages and defective angiogenesis in the diencephalon at 11 dpc, and become non-viable between 11.5 and 12.5 dpc. Loss-of-function mutant resulting in impaired sialic acid biosynthesis. | ||||
Sequence: P → R |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 32 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000095717 | 1-722 | Bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase | |||
Sequence: MEKNGNNRKLRVCVATCNRADYSKLAPIMFGIKTEPAFFELDVVVLGSHLIDDYGNTYRMIEQDDFDINTRLHTIVRGEDEAAMVESVGLALVKLPDVLNRLKPDIMIVHGDRFDALALATSAALMNIRILHIEGGEVSGTIDDSIRHAITKLAHYHVCCTRSAEQHLISMCEDHDRILLAGCPSYDKLLSAKNKDYMSIIRMWLGDDVKCKDYIVALQHPVTTDIKHSIKMFELTLDALISFNKRTLVLFPNIDAGSKEMVRVMRKKGIEHHPNFRAVKHVPFDQFIQLVAHAGCMIGNSSCGVREVGAFGTPVINLGTRQIGRETGENVLHVRDADTQDKILQALHLQFGKQYPCSKIYGDGNAVPRILKFLKSIDLQEPLQKKFCFPPVKENISQDIDHILETLSALAVDLGGTNLRVAIVSMKGEIVKKYTQFNPKTYEERISLILQMCVEAAAEAVKLNCRILGVGISTGGRVNPQEGVVLHSTKLIQEWNSVDLRTPLSDTLHLPVWVDNDGNCAAMAERKFGQGKGQENFVTLITGTGIGGGIIHQHELIHGSSFCAAELGHLVVSLDGPDCSCGSHGCIEAYASGMALQREAKKLHDEDLLLVEGMSVPKDEAVGALHLIQAAKLGNVKAQSILRTAGTALGLGVVNILHTMNPSLVILSGVLASHYIHIVKDVIRQQALSSVQDVDVVVSDLVDPALLGAASMVLDYTTRRIH |
Post-translational modification
Phosphorylated. Phosphorylation by PKC activates the UDP-N-acetylglucosamine 2-epimerase activity.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Widely expressed. Highest expression in liver. Also found at high levels in lung, brain and kidney.
Developmental stage
In the embryo, expressed at day 7 dpc, 11 dpc and 15 dpc.
Gene expression databases
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-? | UDP-N-acetylglucosamine 2-epimerase | ||||
Region | 406-722 | N-acetylmannosamine kinase | ||||
Sequence: TLSALAVDLGGTNLRVAIVSMKGEIVKKYTQFNPKTYEERISLILQMCVEAAAEAVKLNCRILGVGISTGGRVNPQEGVVLHSTKLIQEWNSVDLRTPLSDTLHLPVWVDNDGNCAAMAERKFGQGKGQENFVTLITGTGIGGGIIHQHELIHGSSFCAAELGHLVVSLDGPDCSCGSHGCIEAYASGMALQREAKKLHDEDLLLVEGMSVPKDEAVGALHLIQAAKLGNVKAQSILRTAGTALGLGVVNILHTMNPSLVILSGVLASHYIHIVKDVIRQQALSSVQDVDVVVSDLVDPALLGAASMVLDYTTRRIH |
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.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length722
- Mass (Da)79,199
- Last updated2001-12-01 v1
- Checksum0DFDD681BFD17984
Computationally mapped potential isoform sequences
There are 10 potential isoforms mapped to this entry
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 566-567 | in Ref. 1; CAB36908 | ||||
Sequence: EL → DV | ||||||
Sequence conflict | 623 | in Ref. 1; CAB36908 | ||||
Sequence: G → V |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AJ132236 EMBL· GenBank· DDBJ | CAB36908.1 EMBL· GenBank· DDBJ | mRNA | ||
BC015277 EMBL· GenBank· DDBJ | AAH15277.1 EMBL· GenBank· DDBJ | mRNA | ||
BC051254 EMBL· GenBank· DDBJ | AAH51254.1 EMBL· GenBank· DDBJ | mRNA | ||
AK033507 EMBL· GenBank· DDBJ | BAC28328.1 EMBL· GenBank· DDBJ | mRNA | ||
AK033691 EMBL· GenBank· DDBJ | BAC28432.1 EMBL· GenBank· DDBJ | mRNA |