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Protein

Bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase

Gene

Gne

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).By similarity

Catalytic activityi

UDP-N-acetyl-alpha-D-glucosamine + H2O = N-acetyl-D-mannosamine + UDP.1 Publication
ATP + N-acyl-D-mannosamine = ADP + N-acyl-D-mannosamine 6-phosphate.1 Publication

Enzyme regulationi

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.By similarity1 Publication

Pathwayi: N-acetylneuraminate biosynthesis

This protein is involved in the pathway N-acetylneuraminate biosynthesis, which is part of Amino-sugar metabolism.
View all proteins of this organism that are known to be involved in the pathway N-acetylneuraminate biosynthesis and in Amino-sugar metabolism.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei477 – 4771SubstrateBy similarity
Binding sitei489 – 4891SubstrateBy similarity
Active sitei517 – 5171By similarity
Binding sitei517 – 5171SubstrateBy similarity
Binding sitei566 – 5661SubstrateBy similarity
Metal bindingi569 – 5691ZincBy similarity
Binding sitei569 – 5691SubstrateBy similarity
Metal bindingi579 – 5791ZincBy similarity
Metal bindingi581 – 5811ZincBy similarity
Metal bindingi586 – 5861ZincBy similarity
Binding sitei588 – 5881SubstrateBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi411 – 42010ATPBy similarity
Nucleotide bindingi543 – 55210ATPBy similarity

GO - Molecular functioni

GO - Biological processi

  • carbohydrate phosphorylation Source: GOC
  • N-acetylglucosamine biosynthetic process Source: UniProtKB-UniPathway
  • N-acetylneuraminate biosynthetic process Source: RGD
  • UDP-N-acetylglucosamine metabolic process Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase

Keywords - Ligandi

ATP-binding, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

BioCyciMetaCyc:MONOMER-14506.
BRENDAi5.1.3.14. 5301.
ReactomeiR-RNO-4085001. Sialic acid metabolism.
SABIO-RKO35826.
UniPathwayiUPA00630.

Names & Taxonomyi

Protein namesi
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:
UDP-N-acetylglucosamine 2-epimerase (hydrolyzing) (EC:3.2.1.183)
Alternative name(s):
UDP-GlcNAc-2-epimerase
Uridine diphosphate-N-acetylglucosamine-2-epimerase
N-acetylmannosamine kinase (EC:2.7.1.60)
Alternative name(s):
ManAc kinase
Gene namesi
Name:Gne
Synonyms:Glcne
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 5

Organism-specific databases

RGDi69239. Gne.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi49 – 491H → A: Does not affect kinase activity; almost complete loss of epimerase activity; does not interfere with enzyme oligomerization. 1 Publication
Mutagenesisi110 – 1101H → A: Does not affect kinase activity; almost complete loss of epimerase activity; partial reduction of the dimerization process. 1 Publication
Mutagenesisi132 – 1321H → A: Does not affect kinase activity; almost complete loss of epimerase activity; partial reduction of the dimerization process. 1 Publication
Mutagenesisi155 – 1551H → A: Does not affect kinase activity; almost complete loss of epimerase activity; strong reduction of the dimerization process. 1 Publication
Mutagenesisi157 – 1571H → A: Does not affect kinase activity; almost complete loss of epimerase activity; strong reduction of the dimerization process. 1 Publication
Mutagenesisi413 – 4131D → 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. 1 Publication
Mutagenesisi420 – 4201R → 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. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 722722Bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinasePRO_0000095718Add
BLAST

Post-translational modificationi

Phosphorylated by PKC.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiO35826.
PRIDEiO35826.

PTM databases

PhosphoSiteiO35826.

Expressioni

Tissue specificityi

Widely expressed. Highest expression is observed in liver.2 Publications

Gene expression databases

ExpressionAtlasiO35826. baseline and differential.
GenevisibleiO35826. RN.

Interactioni

Subunit structurei

Homodimer and homohexamer.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
ZBTB16Q055162EBI-7109445,EBI-711925From a different organism.

Protein-protein interaction databases

BioGridi250408. 5 interactions.
IntActiO35826. 5 interactions.
MINTiMINT-4051080.
STRINGi10116.ENSRNOP00000019532.

Structurei

3D structure databases

ProteinModelPortaliO35826.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – ?UDP-N-acetylglucosamine 2-epimerase
Regioni406 – 722317N-acetylmannosamine kinaseBy similarityAdd
BLAST

Sequence similaritiesi

In the N-terminal section; belongs to the UDP-N-acetylglucosamine 2-epimerase family.Curated
In the C-terminal section; belongs to the ROK (NagC/XylR) family.Curated

Phylogenomic databases

eggNOGiENOG410IE3W. Eukaryota.
COG0381. LUCA.
COG1940. LUCA.
GeneTreeiENSGT00390000017246.
HOGENOMiHOG000008254.
HOVERGENiHBG051733.
InParanoidiO35826.
KOiK12409.
OMAiIAMCEDH.
OrthoDBiEOG73V6JN.
PhylomeDBiO35826.

Family and domain databases

InterProiIPR000600. ROK.
IPR020004. UDP-GlcNAc_Epase.
IPR003331. UDP_GlcNAc_Epimerase_2_dom.
[Graphical view]
PfamiPF02350. Epimerase_2. 1 hit.
PF00480. ROK. 1 hit.
[Graphical view]
TIGRFAMsiTIGR03568. NeuC_NnaA. 1 hit.

Sequencei

Sequence statusi: Complete.

O35826-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEKNGNNRKL RVCVATCNRA DYSKLAPIMF GIKTEPAFFE LDVVVLGSHL
60 70 80 90 100
IDDYGNTYRM IEQDDFDINT RLHTIVRGED EAAMVESVGL ALVKLPDVLN
110 120 130 140 150
RLKPDIMIVH GDRFDALALA TSAALMNIRI LHIEGGEVSG TIDDSIRHAI
160 170 180 190 200
TKLAHYHVCC TRSAEQHLIS MCEDHDRILL AGCPSYDKLL SAKNKDYMSI
210 220 230 240 250
IRMWLGDDVK CKDYIVALQH PVTTDIKHSI KMFELTLDAL ISFNKRTLVL
260 270 280 290 300
FPNIDAGSKE MVRVMRKKGI EHHPNFRAVK HVPFDQFIQL VAHAGCMIGN
310 320 330 340 350
SSCGVREVGA FGTPVINLGT RQIGRETGEN VLHVRDADTQ DKILQALHLQ
360 370 380 390 400
FGKQYPCSKI YGDGNAVPRI LKFLKSIDLQ EPLQKKFCFP PVKENISQDI
410 420 430 440 450
DHILETLSAL AVDLGGTNLR VAIVSMKGEI VKKYTQFNPK TYEERISLIL
460 470 480 490 500
QMCVEAAAEA VKLNCRILGV GISTGGRVNP QEGVVLHSTK LIQEWNSVDL
510 520 530 540 550
RTPLSDTLHL PVWVDNDGNC AAMAERKFGQ GKGQENFVTL ITGTGIGGGI
560 570 580 590 600
IHQHELIHGS SFCAAELGHL VVSLDGPDCS CGSHGCIEAY ASGMALQREA
610 620 630 640 650
KKLHDEDLLL VEGMSVPKDE AVGALHLIQA AKLGNVKAQS ILRTAGTALG
660 670 680 690 700
LGVVNILHTM NPSLVILSGV LASHYIHIVR DVIRQQALSS VQDVDVVVSD
710 720
LVDPALLGAA SMVLDYTTRR IH
Length:722
Mass (Da):79,227
Last modified:January 1, 1998 - v1
Checksum:i0DFDC84E833C7984
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y07744 mRNA. Translation: CAA69024.1.
BC062011 mRNA. Translation: AAH62011.1.
RefSeqiNP_446217.1. NM_053765.2.
XP_006238070.1. XM_006238008.1.
XP_006238071.1. XM_006238009.2.
UniGeneiRn.18753.

Genome annotation databases

EnsembliENSRNOT00000019532; ENSRNOP00000019532; ENSRNOG00000014365.
GeneIDi114711.
KEGGirno:114711.
UCSCiRGD:69239. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y07744 mRNA. Translation: CAA69024.1.
BC062011 mRNA. Translation: AAH62011.1.
RefSeqiNP_446217.1. NM_053765.2.
XP_006238070.1. XM_006238008.1.
XP_006238071.1. XM_006238009.2.
UniGeneiRn.18753.

3D structure databases

ProteinModelPortaliO35826.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi250408. 5 interactions.
IntActiO35826. 5 interactions.
MINTiMINT-4051080.
STRINGi10116.ENSRNOP00000019532.

PTM databases

PhosphoSiteiO35826.

Proteomic databases

PaxDbiO35826.
PRIDEiO35826.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000019532; ENSRNOP00000019532; ENSRNOG00000014365.
GeneIDi114711.
KEGGirno:114711.
UCSCiRGD:69239. rat.

Organism-specific databases

CTDi10020.
RGDi69239. Gne.

Phylogenomic databases

eggNOGiENOG410IE3W. Eukaryota.
COG0381. LUCA.
COG1940. LUCA.
GeneTreeiENSGT00390000017246.
HOGENOMiHOG000008254.
HOVERGENiHBG051733.
InParanoidiO35826.
KOiK12409.
OMAiIAMCEDH.
OrthoDBiEOG73V6JN.
PhylomeDBiO35826.

Enzyme and pathway databases

UniPathwayiUPA00630.
BioCyciMetaCyc:MONOMER-14506.
BRENDAi5.1.3.14. 5301.
ReactomeiR-RNO-4085001. Sialic acid metabolism.
SABIO-RKO35826.

Miscellaneous databases

NextBioi618845.
PROiO35826.

Gene expression databases

ExpressionAtlasiO35826. baseline and differential.
GenevisibleiO35826. RN.

Family and domain databases

InterProiIPR000600. ROK.
IPR020004. UDP-GlcNAc_Epase.
IPR003331. UDP_GlcNAc_Epimerase_2_dom.
[Graphical view]
PfamiPF02350. Epimerase_2. 1 hit.
PF00480. ROK. 1 hit.
[Graphical view]
TIGRFAMsiTIGR03568. NeuC_NnaA. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
    Cited for: CATALYTIC ACTIVITY, 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] [Europe PMC] [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] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF HIS-49; HIS-110; HIS-132; HIS-155; HIS-157; ASP-413 AND ARG-420.

Entry informationi

Entry nameiGLCNE_RAT
AccessioniPrimary (citable) accession number: O35826
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 15, 2004
Last sequence update: January 1, 1998
Last modified: February 17, 2016
This is version 118 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Allosteric enzyme, Complete proteome, Direct protein sequencing, Multifunctional enzyme, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.