O35826 (GLCNE_RAT) Reviewed, UniProtKB/Swiss-Prot

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. UDP-N-acetylglucosamine 2-epimerase
   EC=5.1.3.14
   Alternative name(s):
   UDP-GlcNAc-2-epimerase
   Uridine diphosphate-N-acetylglucosamine-2-epimerase
2. N-acetylmannosamine kinase
   EC=2.7.1.60
   Alternative name(s):
   ManAc kinase

Gene names

Name:	Gne
Synonyms:	Glcne

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	722 AA.
Sequence status	Complete.
Protein existence	Evidence at protein 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 By similarity; 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. Ref.3
Pathway	Amino-sugar metabolism; N-acetylneuraminate biosynthesis.
Subunit structure	Homodimer and homohexamer. Ref.3
Subcellular location	Cytoplasm Ref.1 Ref.3.
Tissue specificity	Widely expressed. Highest expression is observed in liver. Ref.1 Ref.4
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
Ligand	ATP-binding Nucleotide-binding
Molecular function	Isomerase Kinase Transferase
PTM	Phosphoprotein
Technical term	Allosteric enzyme Complete proteome Direct protein sequencing Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Biological process	N-acetylneuraminate biosynthetic process Traceable author statement. Source: RGD UDP-N-acetylglucosamine metabolic process Inferred from electronic annotation. Source: InterPro lipopolysaccharide biosynthetic process Inferred from electronic annotation. Source: InterPro
Cellular component	cytosol Inferred from direct assay Ref.1. Source: RGD
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW N-acylmannosamine kinase activity Inferred from direct assay Ref.1. Source: RGD UDP-N-acetylglucosamine 2-epimerase activity Inferred from direct assay Ref.1. Source: RGD
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_0000095718
Regions
	Nucleotide binding	411 – 418	8	ATP Potential
	Nucleotide binding	545 – 552	8	ATP Potential
	Region	1 – ?		UDP-N-acetylglucosamine 2-epimerase
	Region	406 – 722	317	N-acetylmannosamine kinase By similarity
Experimental info
	Mutagenesis	49	1	H → A: Does not affect kinase activity; almost complete loss of epimerase activity; does not interfere with enzyme oligomerization. Ref.5
	Mutagenesis	110	1	H → A: Does not affect kinase activity; almost complete loss of epimerase activity; partial reduction of the dimerization process. Ref.5
	Mutagenesis	132	1	H → A: Does not affect kinase activity; almost complete loss of epimerase activity; partial reduction of the dimerization process. Ref.5
	Mutagenesis	155	1	H → A: Does not affect kinase activity; almost complete loss of epimerase activity; strong reduction of the dimerization process. Ref.5
	Mutagenesis	157	1	H → A: Does not affect kinase activity; almost complete loss of epimerase activity; strong reduction of the dimerization process. Ref.5
	Mutagenesis	413	1	D → K or N: Does not affect epimerase activity; does not affect feedback inhibition by CMP-Neu5Ac; almost complete loss of kinase activity; does not interfere with oligomerization. Ref.5
	Mutagenesis	420	1	R → M: Does not affect epimerase activity; does not affect feedback inhibition by CMP-Neu5Ac; almost complete loss of kinase activity; does not interfere with oligomerization. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	O35826 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: 0DFDC84E833C7984	FASTA	722	79,227
	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 QEGVVLHSTK 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 AVGALHLIQA AKLGNVKAQS ILRTAGTALG LGVVNILHTM 670 680 690 700 710 720 NPSLVILSGV LASHYIHIVR DVIRQQALSS VQDVDVVVSD LVDPALLGAA SMVLDYTTRR IH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A bifunctional enzyme catalyzes the first two steps in N-acetylneuraminic acid biosynthesis of rat liver. Molecular cloning and functional expression of UDP-N-acetyl-glucosamine 2-epimerase/N-acetylmannosamine kinase." Staesche R., Hinderlich S., Weise C., Effertz K., Lucka L., Moormann P., Reutter W. J. Biol. Chem. 272:24319-24324(1997) [PubMed: 9305888] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 153-162; 269-277; 309-321; 434-441 AND 491-500, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Tissue: Liver.
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Prostate.
[3]	"A bifunctional enzyme catalyzes the first two steps in N-acetylneuraminic acid biosynthesis of rat liver. Purification and characterization of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase." Hinderlich S., Staesche R., Zeitler R., Reutter W. J. Biol. Chem. 272:24313-24318(1997) [PubMed: 9305887] [Abstract] Cited for: SUBCELLULAR LOCATION, SUBUNIT, ENZYME REGULATION.
[4]	"Tissue expression and amino acid sequence of murine UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase." Horstkorte R., Noehring S., Wiechens N., Schwarzkopf M., Danker K., Reutter W., Lucka L. Eur. J. Biochem. 260:923-927(1999) [PubMed: 10103025] [Abstract] Cited for: TISSUE SPECIFICITY.
[5]	"Selective loss of either the epimerase or kinase activity of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase due to site-directed mutagenesis based on sequence alignments." Effertz K., Hinderlich S., Reutter W. J. Biol. Chem. 274:28771-28778(1999) [PubMed: 10497249] [Abstract] Cited for: MUTAGENESIS OF HIS-49; HIS-110; HIS-132; HIS-155; HIS-157; ASP-413 AND ARG-420.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	Y07744 mRNA. Translation: CAA69024.1. BC062011 mRNA. Translation: AAH62011.1.
IPI	IPI00213065.
RefSeq	NP_446217.1. NM_053765.2.
UniGene	Rn.18753.
3D structure databases
ProteinModelPortal	O35826.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-4051080.
STRING	O35826.
PTM databases
PhosphoSite	O35826.
Proteomic databases
PRIDE	O35826.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000019532; ENSRNOP00000019532; ENSRNOG00000014365.
GeneID	114711.
KEGG	rno:114711.
NMPDR	fig|10116.3.peg.23058.
UCSC	NM_053765. rat.
Organism-specific databases
CTD	10020.
RGD	69239. Gne.
Phylogenomic databases
eggNOG	roNOG15288.
GeneTree	ENSGT00390000017246.
HOVERGEN	HBG051733.
InParanoid	O35826.
OrthoDB	EOG4QFWCN.
PhylomeDB	O35826.
Enzyme and pathway databases
BioCyc	MetaCyc:MONOMER-14506.
Gene expression databases
Genevestigator	O35826.
GermOnline	ENSRNOG00000014365. Rattus norvegicus.
Family and domain databases
InterPro	IPR001312. Hexokinase. IPR000600. ROK. IPR020004. UDP-GlcNAc_Epase. IPR003331. UDP_GlcNAc_Epimerase_2. [Graphical view]
KO	K12409.
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...
Other
NextBio	618845.

Entry information

Entry name

GLCNE_RAT

Accession

Primary (citable) accession number: O35826

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 15, 2004
Last sequence update:	January 1, 1998
Last modified:	November 16, 2011
This is version 90 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program