Q9Y223 · GLCNE_HUMAN
- 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:10334995, PubMed:11326336, PubMed:14707127, PubMed:16503651, PubMed:2808337, 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 (PubMed:10334995, PubMed:14707127).
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 = 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 (PubMed:26980148, PubMed:2808337).
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).
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.
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 | 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 | 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
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ9Y223
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
Sialuria (SIALURIA)
- Note
- DescriptionIn 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.
- See alsoMIM:269921
Natural variants in SIALURIA
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_017950 | 263 | R>L | in SIALURIA; strong reduction of feedback inhibition by CMP-Neu5Ac; dbSNP:rs121908623 | |
VAR_017951 | 266 | R>Q | in SIALURIA; abolishes feedback inhibition by CMP-Neu5Ac; dbSNP:rs121908622 |
Nonaka myopathy (NM)
- Note
- DescriptionAn autosomal recessive myopathy characterized by early adult onset and progressive distal muscle weakness that preferentially affects the anterior tibial muscles, usually sparing the quadriceps femoris. Some individuals may have involvement of the upper limbs or proximal muscles. Muscle biopsy reveals presence of rimmed vacuoles.
- See alsoMIM:605820
Natural variants in NM
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_087335 | 13 | C>S | in NM; decreased UDP-N-acetylglucosamine 2-epimerase activity; no effect on N-acylmannosamine kinase activity; dbSNP:rs1209266607 | |
VAR_021771 | 27 | P>S | in NM; dbSNP:rs1554664064 | |
VAR_017945 | 36 | P>L | in NM | |
VAR_021772 | 132 | H>Q | in NM; decreased UDP-N-acetylglucosamine 2-epimerase activity; impaired homohexamers formation | |
VAR_021773 | 162 | R>C | in NM; dbSNP:rs769215411 | |
VAR_021774 | 171 | M>V | in NM; dbSNP:rs121908634 | |
VAR_021775 | 176 | D>V | in NM; decreased UDP-N-acetylglucosamine 2-epimerase activity; no effect on N-acylmannosamine kinase activity; impaired homohexamers formation; dbSNP:rs139425890 | |
VAR_021776 | 177 | R>C | in NM; decreased UDP-N-acetylglucosamine 2-epimerase activity; impaired homohexamers formation; dbSNP:rs539332585 | |
VAR_017946 | 200 | I>F | in NM; uncertain significance; dbSNP:rs369328625 | |
VAR_021777 | 206 | G>S | in NM; moderate phenotype with unusual involvement of quadriceps; dbSNP:rs766266918 | |
VAR_021778 | 216 | V>A | in NM; dbSNP:rs779694939 | |
VAR_017947 | 225 | D>N | in NM; dbSNP:rs121908630 | |
VAR_017948 | 246 | R>Q | in NM; dbSNP:rs121908629 | |
VAR_017949 | 246 | R>W | in NM; dbSNP:rs773729410 | |
VAR_017953 | 303 | C>V | in NM; requires 2 nucleotide substitutions; dbSNP:rs121908633 | |
VAR_021779 | 306 | R>Q | in NM; dbSNP:rs1455785164 | |
VAR_021780 | 331 | V>A | in NM; decreased UDP-N-acetylglucosamine 2-epimerase activity; no effect on N-acylmannosamine kinase activity; impaired homohexamers formation | |
VAR_017954 | 378 | D>Y | in NM; decreased UDP-N-acetylglucosamine 2-epimerase activity; impaired homohexamers formation; dbSNP:rs199877522 | |
VAR_017955 | 460 | A>V | in NM; dbSNP:rs121908631 | |
VAR_021781 | 472 | I>T | in NM; decreased UDP-N-acetylglucosamine 2-epimerase activity; decreased N-acylmannosamine kinase activity corresponding to less than 10% of wild-type activity | |
VAR_021782 | 519 | N>S | in NM and THC12; likely pathogenic; decreased UDP-N-acetylglucosamine 2-epimerase activity; decreased N-acylmannosamine kinase activity; dbSNP:rs1554658910 | |
VAR_017956 | 524 | A>V | in NM; decreased UDP-N-acetylglucosamine 2-epimerase activity corresponding to less than 10% of wild-type activity; decreased N-acylmannosamine kinase activity; impaired homohexamers formation; dbSNP:rs764698870 | |
VAR_017957 | 528 | F>C | in NM; decreased N-acylmannosamine kinase activity; dbSNP:rs986773986 | |
VAR_017958 | 557 | I>T | in NM; dbSNP:rs886043979 | |
VAR_017959 | 572 | V>L | in NM and THC12; likely pathogenic; mildly decreased UDP-N-acetylglucosamine 2-epimerase activity; decreased N-acylmannosamine kinase activity corresponding to less than 10% of wild-type activity; does not affect homohexamers formation; dbSNP:rs121908632 | |
VAR_017960 | 576 | G>E | in NM; decreased UDP-N-acetylglucosamine 2-epimerase activity; decreased N-acylmannosamine kinase activity; dbSNP:rs121908625 | |
VAR_017961 | 587 | I>T | in NM; decreased UDP-N-acetylglucosamine 2-epimerase activity; decreased N-acylmannosamine kinase activity; dbSNP:rs748949603 | |
VAR_021783 | 600 | A>T | in NM; dbSNP:rs387906347 | |
VAR_021784 | 630 | A>T | in NM; decreased N-acylmannosamine kinase activity; does not affect homohexamers formation; dbSNP:rs1382191649 | |
VAR_017962 | 631 | A>T | in NM; dbSNP:rs121908626 | |
VAR_017963 | 631 | A>V | in NM; does not affect homohexamers formation; dbSNP:rs62541771 | |
VAR_017964 | 675 | Y>H | in NM; dbSNP:rs1191857860 | |
VAR_017965 | 696 | V>M | in NM; dbSNP:rs121908627 | |
VAR_087336 | 708 | G>S | in NM and THC12; likely pathogenic; decreased UDP-N-acetylglucosamine 2-epimerase activity; severely decreased N-acylmannosamine kinase activity; dbSNP:rs1554657922 | |
VAR_017966 | 712 | M>T | in NM; decreased N-acylmannosamine kinase activity; dbSNP:rs28937594 |
Thrombocytopenia 12 with or without myopathy (THC12)
- Note
- DescriptionA form of thrombocytopenia, a hematologic disorder defined by a decrease in the number of platelets in circulating blood, resulting in the potential for increased bleeding and decreased ability for clotting. THC12 is an autosomal recessive form manifesting from infancy or early childhood with bleeding episodes. Clinical features include petechiae, easy bruising, epistaxis, hematomas, menorrhagia, and increased bleeding after trauma or surgery. Rare patients may have thrombocytopenia without bleeding. Some affected individuals have myopathic features, usually apparent in the second or third decades of life.
- See alsoMIM:620757
Natural variants in THC12
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_089477 | 157 | H>Y | in THC12; likely pathogenic | |
VAR_089478 | 413 | D>Y | in THC12; likely pathogenic | |
VAR_089479 | 417 | T>M | in THC12; likely pathogenic | |
VAR_089481 | 420 | R>Q | in THC12; likely pathogenic | |
VAR_089480 | 420-722 | missing | in THC12; likely pathogenic | |
VAR_089482 | 475 | G>F | in THC12; likely pathogenic; requires 2 nucleotide substitutions | |
VAR_089483 | 485 | V>R | in THC12; uncertain significance; reduced protein abundance in homozygous patient cells; requires 2 nucleotide substitutions | |
VAR_089484 | 486 | L>P | in THC12; uncertain significance | |
VAR_021782 | 519 | N>S | in NM and THC12; likely pathogenic; decreased UDP-N-acetylglucosamine 2-epimerase activity; decreased N-acylmannosamine kinase activity; dbSNP:rs1554658910 | |
VAR_089485 | 544 | T>R | in THC12; uncertain significance; reduced protein abundance in homozygous patient cells | |
VAR_089486 | 563 | C>Y | in THC12; likely pathogenic; results in severely decreased cell surface sialylation | |
VAR_017959 | 572 | V>L | in NM and THC12; likely pathogenic; mildly decreased UDP-N-acetylglucosamine 2-epimerase activity; decreased N-acylmannosamine kinase activity corresponding to less than 10% of wild-type activity; does not affect homohexamers formation; dbSNP:rs121908632 | |
VAR_089487 | 704 | P>R | in THC12; likely pathogenic; the orthologous mutation in mouse embryos results in cerebrospinal hemorrhages and defective angiogenesis; results in loss of cell surface sialylation | |
VAR_087336 | 708 | G>S | in NM and THC12; likely pathogenic; decreased UDP-N-acetylglucosamine 2-epimerase activity; severely decreased N-acylmannosamine kinase activity; dbSNP:rs1554657922 |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_087335 | 13 | in NM; decreased UDP-N-acetylglucosamine 2-epimerase activity; no effect on N-acylmannosamine kinase activity; dbSNP:rs1209266607 | |||
Sequence: C → S | ||||||
Natural variant | VAR_021771 | 27 | in NM; dbSNP:rs1554664064 | |||
Sequence: P → S | ||||||
Natural variant | VAR_017945 | 36 | in NM | |||
Sequence: P → L | ||||||
Natural variant | VAR_021772 | 132 | in NM; decreased UDP-N-acetylglucosamine 2-epimerase activity; impaired homohexamers formation | |||
Sequence: H → Q | ||||||
Natural variant | VAR_089477 | 157 | in THC12; likely pathogenic | |||
Sequence: H → Y | ||||||
Natural variant | VAR_021773 | 162 | in NM; dbSNP:rs769215411 | |||
Sequence: R → C | ||||||
Natural variant | VAR_021774 | 171 | in NM; dbSNP:rs121908634 | |||
Sequence: M → V | ||||||
Natural variant | VAR_021775 | 176 | in NM; decreased UDP-N-acetylglucosamine 2-epimerase activity; no effect on N-acylmannosamine kinase activity; impaired homohexamers formation; dbSNP:rs139425890 | |||
Sequence: D → V | ||||||
Natural variant | VAR_021776 | 177 | in NM; decreased UDP-N-acetylglucosamine 2-epimerase activity; impaired homohexamers formation; dbSNP:rs539332585 | |||
Sequence: R → C | ||||||
Natural variant | VAR_017946 | 200 | in NM; uncertain significance; dbSNP:rs369328625 | |||
Sequence: I → F | ||||||
Natural variant | VAR_021777 | 206 | in NM; moderate phenotype with unusual involvement of quadriceps; dbSNP:rs766266918 | |||
Sequence: G → S | ||||||
Natural variant | VAR_021778 | 216 | in NM; dbSNP:rs779694939 | |||
Sequence: V → A | ||||||
Natural variant | VAR_017947 | 225 | in NM; dbSNP:rs121908630 | |||
Sequence: D → N | ||||||
Natural variant | VAR_017948 | 246 | in NM; dbSNP:rs121908629 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_017949 | 246 | in NM; dbSNP:rs773729410 | |||
Sequence: R → W | ||||||
Natural variant | VAR_017950 | 263 | in SIALURIA; strong reduction of feedback inhibition by CMP-Neu5Ac; dbSNP:rs121908623 | |||
Sequence: R → L | ||||||
Natural variant | VAR_017951 | 266 | in SIALURIA; abolishes feedback inhibition by CMP-Neu5Ac; dbSNP:rs121908622 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_017952 | 266 | in sialuria; dbSNP:rs121908621 | |||
Sequence: R → W | ||||||
Natural variant | VAR_017953 | 303 | in NM; requires 2 nucleotide substitutions; dbSNP:rs121908633 | |||
Sequence: C → V | ||||||
Natural variant | VAR_021779 | 306 | in NM; dbSNP:rs1455785164 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_021780 | 331 | in NM; decreased UDP-N-acetylglucosamine 2-epimerase activity; no effect on N-acylmannosamine kinase activity; impaired homohexamers formation | |||
Sequence: V → A | ||||||
Natural variant | VAR_017954 | 378 | in NM; decreased UDP-N-acetylglucosamine 2-epimerase activity; impaired homohexamers formation; dbSNP:rs199877522 | |||
Sequence: D → Y | ||||||
Natural variant | VAR_089478 | 413 | in THC12; likely pathogenic | |||
Sequence: D → Y | ||||||
Natural variant | VAR_089479 | 417 | in THC12; likely pathogenic | |||
Sequence: T → M | ||||||
Natural variant | VAR_089481 | 420 | in THC12; likely pathogenic | |||
Sequence: R → Q | ||||||
Natural variant | VAR_089480 | 420-722 | in THC12; likely pathogenic | |||
Sequence: Missing | ||||||
Natural variant | VAR_017955 | 460 | in NM; dbSNP:rs121908631 | |||
Sequence: A → V | ||||||
Natural variant | VAR_021781 | 472 | in NM; decreased UDP-N-acetylglucosamine 2-epimerase activity; decreased N-acylmannosamine kinase activity corresponding to less than 10% of wild-type activity | |||
Sequence: I → T | ||||||
Natural variant | VAR_089482 | 475 | in THC12; likely pathogenic; requires 2 nucleotide substitutions | |||
Sequence: G → F | ||||||
Natural variant | VAR_089483 | 485 | in THC12; uncertain significance; reduced protein abundance in homozygous patient cells; requires 2 nucleotide substitutions | |||
Sequence: V → R | ||||||
Natural variant | VAR_089484 | 486 | in THC12; uncertain significance | |||
Sequence: L → P | ||||||
Mutagenesis | 517 | Loss of N-acylmannosamine kinase activity. Decreased affinity for N-acyl-D-mannosamine. No effect on structure. | ||||
Sequence: D → A or N | ||||||
Natural variant | VAR_021782 | 519 | in NM and THC12; likely pathogenic; decreased UDP-N-acetylglucosamine 2-epimerase activity; decreased N-acylmannosamine kinase activity; dbSNP:rs1554658910 | |||
Sequence: N → S | ||||||
Natural variant | VAR_017956 | 524 | in NM; decreased UDP-N-acetylglucosamine 2-epimerase activity corresponding to less than 10% of wild-type activity; decreased N-acylmannosamine kinase activity; impaired homohexamers formation; dbSNP:rs764698870 | |||
Sequence: A → V | ||||||
Natural variant | VAR_017957 | 528 | in NM; decreased N-acylmannosamine kinase activity; dbSNP:rs986773986 | |||
Sequence: F → C | ||||||
Natural variant | VAR_089485 | 544 | in THC12; uncertain significance; reduced protein abundance in homozygous patient cells | |||
Sequence: T → R | ||||||
Natural variant | VAR_017958 | 557 | in NM; dbSNP:rs886043979 | |||
Sequence: I → T | ||||||
Natural variant | VAR_089486 | 563 | in THC12; likely pathogenic; results in severely decreased cell surface sialylation | |||
Sequence: C → Y | ||||||
Natural variant | VAR_017959 | 572 | in NM and THC12; likely pathogenic; mildly decreased UDP-N-acetylglucosamine 2-epimerase activity; decreased N-acylmannosamine kinase activity corresponding to less than 10% of wild-type activity; does not affect homohexamers formation; dbSNP:rs121908632 | |||
Sequence: V → L | ||||||
Natural variant | VAR_017960 | 576 | in NM; decreased UDP-N-acetylglucosamine 2-epimerase activity; decreased N-acylmannosamine kinase activity; dbSNP:rs121908625 | |||
Sequence: G → E | ||||||
Natural variant | VAR_017961 | 587 | in NM; decreased UDP-N-acetylglucosamine 2-epimerase activity; decreased N-acylmannosamine kinase activity; dbSNP:rs748949603 | |||
Sequence: I → T | ||||||
Natural variant | VAR_021783 | 600 | in NM; dbSNP:rs387906347 | |||
Sequence: A → T | ||||||
Natural variant | VAR_021784 | 630 | in NM; decreased N-acylmannosamine kinase activity; does not affect homohexamers formation; dbSNP:rs1382191649 | |||
Sequence: A → T | ||||||
Natural variant | VAR_017962 | 631 | in NM; dbSNP:rs121908626 | |||
Sequence: A → T | ||||||
Natural variant | VAR_017963 | 631 | in NM; does not affect homohexamers formation; dbSNP:rs62541771 | |||
Sequence: A → V | ||||||
Natural variant | VAR_017964 | 675 | in NM; dbSNP:rs1191857860 | |||
Sequence: Y → H | ||||||
Natural variant | VAR_017965 | 696 | in NM; dbSNP:rs121908627 | |||
Sequence: V → M | ||||||
Natural variant | VAR_089487 | 704 | in THC12; likely pathogenic; the orthologous mutation in mouse embryos results in cerebrospinal hemorrhages and defective angiogenesis; results in loss of cell surface sialylation | |||
Sequence: P → R | ||||||
Natural variant | VAR_087336 | 708 | in NM and THC12; likely pathogenic; decreased UDP-N-acetylglucosamine 2-epimerase activity; severely decreased N-acylmannosamine kinase activity; dbSNP:rs1554657922 | |||
Sequence: G → S | ||||||
Natural variant | VAR_017966 | 712 | in NM; decreased N-acylmannosamine kinase activity; dbSNP:rs28937594 | |||
Sequence: M → T |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 772 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000095716 | 1-722 | Bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase | |||
Sequence: MEKNGNNRKLRVCVATCNRADYSKLAPIMFGIKTEPEFFELDVVVLGSHLIDDYGNTYRMIEQDDFDINTRLHTIVRGEDEAAMVESVGLALVKLPDVLNRLKPDIMIVHGDRFDALALATSAALMNIRILHIEGGEVSGTIDDSIRHAITKLAHYHVCCTRSAEQHLISMCEDHDRILLAGCPSYDKLLSAKNKDYMSIIRMWLGDDVKSKDYIVALQHPVTTDIKHSIKMFELTLDALISFNKRTLVLFPNIDAGSKEMVRVMRKKGIEHHPNFRAVKHVPFDQFIQLVAHAGCMIGNSSCGVREVGAFGTPVINLGTRQIGRETGENVLHVRDADTQDKILQALHLQFGKQYPCSKIYGDGNAVPRILKFLKSIDLQEPLQKKFCFPPVKENISQDIDHILETLSALAVDLGGTNLRVAIVSMKGEIVKKYTQFNPKTYEERINLILQMCVEAAAEAVKLNCRILGVGISTGGRVNPREGIVLHSTKLIQEWNSVDLRTPLSDTLHLPVWVDNDGNCAALAERKFGQGKGLENFVTLITGTGIGGGIIHQHELIHGSSFCAAELGHLVVSLDGPDCSCGSHGCIEAYASGMALQREAKKLHDEDLLLVEGMSVPKDEAVGALHLIQAAKLGNAKAQSILRTAGTALGLGVVNILHTMNPSLVILSGVLASHYIHIVKDVIRQQALSSVQDVDVVVSDLVDPALLGAASMVLDYTTRRIY |
Post-translational modification
Phosphorylated. Phosphorylation by PKC activates the UDP-N-acetylglucosamine 2-epimerase activity.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
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.
Gene expression databases
Organism-specific databases
Interaction
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).
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).
Binary interactions
Protein-protein interaction databases
Chemistry
Miscellaneous
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: TLSALAVDLGGTNLRVAIVSMKGEIVKKYTQFNPKTYEERINLILQMCVEAAAEAVKLNCRILGVGISTGGRVNPREGIVLHSTKLIQEWNSVDLRTPLSDTLHLPVWVDNDGNCAALAERKFGQGKGLENFVTLITGTGIGGGIIHQHELIHGSSFCAAELGHLVVSLDGPDCSCGSHGCIEAYASGMALQREAKKLHDEDLLLVEGMSVPKDEAVGALHLIQAAKLGNAKAQSILRTAGTALGLGVVNILHTMNPSLVILSGVLASHYIHIVKDVIRQQALSSVQDVDVVVSDLVDPALLGAASMVLDYTTRRIY |
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 & Isoforms
- Sequence statusComplete
This entry describes 5 isoforms produced by Alternative splicing.
Q9Y223-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- SynonymsGNE1
- Length722
- Mass (Da)79,275
- Last updated1999-11-01 v1
- Checksum4D7D049B06B00077
Q9Y223-2
- Name2
- SynonymsGNE2
- Differences from canonical
- 1-1: M → METYGYLQRESCFQGPHELYFKNLSKRNKQIM
Q9Y223-3
- Name3
- SynonymsGNE3
- Differences from canonical
- 1-55: MEKNGNNRKLRVCVATCNRADYSKLAPIMFGIKTEPEFFELDVVVLGSHLIDDYG → MPIGDCSVAAKPRKQLLCSLFQTTLGYRARASGWKPMVICRGSHAFKDLI
Q9Y223-4
- Name4
- Differences from canonical
- 471-544: Missing
Q9Y223-5
- Name5
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A7I2SU25 | A0A7I2SU25_HUMAN | GNE | 663 |
Sequence caution
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_041027 | 1 | in isoform 2 | |||
Sequence: M → METYGYLQRESCFQGPHELYFKNLSKRNKQIM | ||||||
Alternative sequence | VSP_041028 | 1-55 | in isoform 3 | |||
Sequence: MEKNGNNRKLRVCVATCNRADYSKLAPIMFGIKTEPEFFELDVVVLGSHLIDDYG → MPIGDCSVAAKPRKQLLCSLFQTTLGYRARASGWKPMVICRGSHAFKDLI | ||||||
Alternative sequence | VSP_043975 | 1-59 | in isoform 5 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_043976 | 206-256 | in isoform 5 | |||
Sequence: Missing | ||||||
Sequence conflict | 338 | in Ref. 6; BAH12108 | ||||
Sequence: D → G | ||||||
Sequence conflict | 359 | in Ref. 6; BAH12414 | ||||
Sequence: K → R | ||||||
Sequence conflict | 364 | in Ref. 6; BAH12108 | ||||
Sequence: G → V | ||||||
Sequence conflict | 382 | in Ref. 6; BAH12108 | ||||
Sequence: P → L | ||||||
Alternative sequence | VSP_043474 | 471-544 | in isoform 4 | |||
Sequence: Missing | ||||||
Sequence conflict | 498 | in Ref. 6; BAH12108 | ||||
Sequence: V → A | ||||||
Sequence conflict | 521 | in Ref. 6; BAH12414 | ||||
Sequence: A → V |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AJ238764 EMBL· GenBank· DDBJ | CAB42607.1 EMBL· GenBank· DDBJ | mRNA | ||
AF051852 EMBL· GenBank· DDBJ | AAD32251.1 EMBL· GenBank· DDBJ | mRNA | ||
AF155663 EMBL· GenBank· DDBJ | AAD38197.1 EMBL· GenBank· DDBJ | mRNA | ||
AF317635 EMBL· GenBank· DDBJ | AAG31661.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
EU093084 EMBL· GenBank· DDBJ | ABU55403.1 EMBL· GenBank· DDBJ | mRNA | ||
AK295562 EMBL· GenBank· DDBJ | BAH12108.1 EMBL· GenBank· DDBJ | mRNA | ||
AK296687 EMBL· GenBank· DDBJ | BAH12414.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
AK312539 EMBL· GenBank· DDBJ | BAG35438.1 EMBL· GenBank· DDBJ | mRNA | ||
AM697708 EMBL· GenBank· DDBJ | CAM91424.1 EMBL· GenBank· DDBJ | mRNA | ||
AM697709 EMBL· GenBank· DDBJ | CAM91425.1 EMBL· GenBank· DDBJ | mRNA | ||
AL158830 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471071 EMBL· GenBank· DDBJ | EAW58307.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471071 EMBL· GenBank· DDBJ | EAW58309.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC121179 EMBL· GenBank· DDBJ | AAI21180.1 EMBL· GenBank· DDBJ | mRNA |