Reviewed, UniProtKB/Swiss-Prot Q7TQ49 (GLCNE_CRIGR)

Names and origin

Protein names

Recommended name:
    Bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase
Alternative name(s):
    UDP-GlcNAc-2-epimerase/ManAc kinase
Including the following 2 domains:
    1- Recommended name:
            UDP-N-acetylglucosamine 2-epimerase
              EC=5.1.3.14
        Alternative name(s):
            Uridine diphosphate-N-acetylglucosamine-2-epimerase
            UDP-GlcNAc-2-epimerase
    2- Recommended name:
            N-acetylmannosamine kinase
              EC=2.7.1.60
        Alternative name(s):
            ManAc kinase

Gene names

Name:	GNE
Synonyms:	GLCNE

Organism

Cricetulus griseus (Chinese hamster)

Taxonomic identifier

10029 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	722 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at transcript level.

General annotation (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. 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 structure	Homodimer and homohexamer.
Subcellular location	Cytoplasm By similarity.
Post-translational modification	Phosphorylated by PKC By similarity.
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.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Isomerase Kinase Transferase
PTM	Phosphoprotein
Technical term	Allosteric enzyme Multifunctional enzyme
Gene Ontology (GO)
Biological process	UDP-N-acetylglucosamine metabolic process Inferred from electronic annotation. Source: InterPro lipopolysaccharide biosynthetic process Inferred from electronic annotation. Source: InterPro
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW N-acylmannosamine kinase activity Inferred from electronic annotation. Source: EC UDP-N-acetylglucosamine 2-epimerase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 722	722	Bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase		PRO_0000095715
Regions
	Nucleotide binding	411 – 418	8	ATP Potential
	Nucleotide binding	545 – 552	8	ATP Potential
	Region	1 – ?		UDP-N-acetylglucosamine 2-epimerase
	Region	? – 722		N-acetylmannosamine kinase
Natural variations
	Natural variant	135	1	G → E in Lec3 cell glycosylation mutants; loss of epimerase activity.

Sequences

	Sequence		Length	Mass (Da)
	Q7TQ49-1 [UniParc]. Last modified October 1, 2003. Version 1. Checksum: 5AC075CA9DAED642	FASTA	722	79,241
	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

References

[1]	"Lec3 Chinese hamster ovary mutants lack UDP-N-acetylglucosamine 2-epimerase activity because of mutations in the epimerase domain of the Gne gene." Hong Y., Stanley P. J. Biol. Chem. 278:53045-53054(2003) [PubMed: 14561743] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT GLU-135.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AB107226 mRNA. Translation: BAC78543.1.
3D structure databases
ModBase	Search...
Phylogenomic databases
HOVERGEN	Q7TQ49.
Enzyme and pathway databases
BRENDA	2.7.1.60. 18. 5.1.3.14. 18.
Family and domain databases
InterPro	IPR001312. Hexokinase. IPR000600. ROK. IPR020004. UDP-GlcNAc_Epase. IPR003331. UDP_GlcNAc_Epimerase_2. [Graphical view]
Pfam	PF02350. Epimerase_2. 1 hit. PF00480. ROK. 1 hit. [Graphical view]
PRINTS	PR00475. HEXOKINASE.
TIGRFAMs	TIGR03568. NeuC_NnaA. 1 hit.
PROSITE	PS01125. ROK. False negative. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

GLCNE_CRIGR

Accession

Primary (citable) accession number: Q7TQ49

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 15, 2004
Last sequence update:	October 1, 2003
Last modified:	June 16, 2009
This is version 38 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)