UDP-N-acetylglucosamine 2-epimerase
     (EC 5.1.3.14)
     (Uridine diphosphate-N-acetylglucosamine-2-epimerase)
     (UDP-GlcNAc-2-epimerase)
N-acetylmannosamine kinase
     (EC 2.7.1.60)
     (ManAc kinase)

Gene name

	Name:	GNE
	Synonyms:	GLCNE

From

Cricetulus griseus (Chinese hamster)

[TaxID: 10029]

Taxonomy

Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; Muroidea; Cricetidae; Cricetinae; Cricetulus.

Protein existence

2: Evidence at transcript level;

References

[1]

NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT GLU-135.
DOI=10.1074/jbc.M309967200; PubMed=14561743 [NCBI, ExPASy, EBI, Israel, Japan]
Hong Y., Stanley P.;
"Lec3 Chinese hamster ovary mutants lack UDP-N-acetylglucosamine 2-epimerase activity because of mutations in the epimerase domain of the Gne gene.";
J. Biol. Chem. 278:53045-53054(2003).

Comments

FUNCTION: Regulates and initiates biosynthesis of N-acetylneuraminic acid (NeuAc), a precursor of sialic acids. Required for normal sialylation in hematopoietic cells. Sialylation is implicated in cell adhesion, signal transduction, tumorigenicity and metastatic behavior of malignant cells. Plays an essential role in early development (By similarity).
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; 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, and the hexamer is fully active for both enzyme activities. Up-regulated after PKC-dependent phosphorylation (By similarity).
PATHWAY: Amino-sugar metabolism; N-acetylneuraminic acid biosynthesis .
SUBUNIT: Homodimer and homohexamer.
SUBCELLULAR LOCATION: Cytoplasm (By similarity).
PTM: Phosphorylated by PKC (By similarity).
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.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

AB107226; BAC78543.1; -; mRNA.

[EMBL / GenBank / DDBJ] [CoDingSequence]

3D structure databases

ModBase

Q7TQ49.

Ontologies

GO:0005737;	Cellular component: cytoplasm (inferred from electronic annotation from UniProtKB-KW).
GO:0009384;	Molecular function: N-acylmannosamine kinase activity (inferred from electronic annotation from EC).
QuickGo view.

Family and domain databases

InterPro

IPR001312; Hexokinase.
IPR000600; ROK.
IPR003331; UDP_GlcNAc_Epimerase_2.
Graphical view of domain structure.

Pfam

PF02350; Epimerase_2; 1.
PF00480; ROK; 1.
Pfam graphical view of domain structure.

PRINTS

PR00475; HEXOKINASE.

PROSITE

PS01125; ROK; FALSE_NEG.

Phylogenomic databases

HOVERGEN

Q7TQ49; -.

Other

UniRef

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

Allosteric enzyme; ATP-binding; Cytoplasm; Isomerase; Kinase; Multifunctional enzyme; Nucleotide-binding; Phosphoprotein; Polymorphism; Transferase.

Features

Feature table viewer

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 722`	`722`	`Bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase.`	`PRO_0000095715`
`NP_BIND`	`411 418`	`8`	`ATP (Potential).`
`NP_BIND`	`545 552`	`8`	`ATP (Potential).`
`REGION`	`1 ?`		`UDP-N-acetylglucosamine 2-epimerase.`
`REGION`	`? 722`		`N-acetylmannosamine kinase.`
`VARIANT`	`135 135`	`1`	`G -> E (in Lec3 cell glycosylation mutants; loss of epimerase activity).`

Sequence information

Length: 722 AA [This is the length of the unprocessed precursor]

Molecular weight: 79241 Da [This is the MW of the unprocessed precursor]

CRC64: 5AC075CA9DAED642 [This is a checksum on the sequence]

        10         20         30         40         50         60 
MEKNGNNRKL RVCVATCNRA DYSKLAPIMF GIKTEPAFFE LDVVVLGSHL IDDYGNTYRM 

        70         80         90        100        110        120 
IEQDDFDINT RLHTIVRGED EAAMVESVGL ALVKLPDVLN RLKPDIMIVH GDRFDALALA 

       130        140        150        160        170        180 
TSAALMNIRI LHIEGGEVSG TIDDSIRHAI TKLAHYHVCC TRSAEQHLIS MCEDHDRILL 

       190        200        210        220        230        240 
AGCPSYDKLL SAKNKDYMSI IRMWLGDDVK CKDYIVALQH PVTTDIKHSI KMFELTLDAL 

       250        260        270        280        290        300 
ISFNKRTLVL FPNIDAGSKE MVRVMRKKGI EHHPNFRAVK HVPFDQFIQL VAHAGCMIGN 

       310        320        330        340        350        360 
SSCGVREVGA FGTPVINLGT RQIGRETGEN VLHVRDADTQ DKILQALHLQ FGKQYPCSKI 

       370        380        390        400        410        420 
YGDGNAVPRI LKFLKSIDLQ EPLQKKFCFP PVKENISQDI DHILETLSAL AVDLGGTNLR 

       430        440        450        460        470        480 
VAIVSMKGEI VKKYTQFNPK TYEERISLIL QMCVEAAAEA VKLNCRILGV GISTGGRVNP 

       490        500        510        520        530        540 
QEGIVLHSTK LIQEWNSVDL RTPLSDTLHL PVWVDNDGNC AAMAERKFGQ GKGQENFVTL 

       550        560        570        580        590        600 
ITGTGIGGGI IHQHELIHGS SFCAAELGHL VVSLDGPDCS CGSHGCIEAY ASGMALQREA 

       610        620        630        640        650        660 
KKLHDEDLLL VEGMSVPKDE PVGALHLIQA AKLGNVKAQN ILRTAGTALG LGVVNILHTM 

       670        680        690        700        710        720 
DPSLVILSGV LASHYIHIVK DVIRQQASSS VQDVDVVVSD LVDPALLGAA SMVLDYTTRR 


IH

Q7TQ49 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
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	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools