GLCNE_RAT
ID GLCNE_RAT Reviewed; 722 AA.
AC O35826;
DT 15-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase;
DE AltName: Full=UDP-GlcNAc-2-epimerase/ManAc kinase;
DE Includes:
DE RecName: Full=UDP-N-acetylglucosamine 2-epimerase (hydrolyzing);
DE EC=3.2.1.183;
DE AltName: Full=UDP-GlcNAc-2-epimerase;
DE AltName: Full=Uridine diphosphate-N-acetylglucosamine-2-epimerase;
DE Includes:
DE RecName: Full=N-acetylmannosamine kinase;
DE EC=2.7.1.60;
DE AltName: Full=ManAc kinase;
GN Name=Gne; Synonyms=Glcne;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 153-162; 269-277; 309-321;
RP 434-441 AND 491-500, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=9305888; DOI=10.1074/jbc.272.39.24319;
RA Staesche R., Hinderlich S., Weise C., Effertz K., Lucka L., Moormann P.,
RA Reutter W.;
RT "A bifunctional enzyme catalyzes the first two steps in N-acetylneuraminic
RT acid biosynthesis of rat liver. Molecular cloning and functional expression
RT of UDP-N-acetyl-glucosamine 2-epimerase/N-acetylmannosamine kinase.";
RL J. Biol. Chem. 272:24319-24324(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, SUBUNIT, AND ACTIVITY REGULATION.
RX PubMed=9305887; DOI=10.1074/jbc.272.39.24313;
RA Hinderlich S., Staesche R., Zeitler R., Reutter W.;
RT "A bifunctional enzyme catalyzes the first two steps in N-acetylneuraminic
RT acid biosynthesis of rat liver. Purification and characterization of UDP-N-
RT acetylglucosamine 2-epimerase/N-acetylmannosamine kinase.";
RL J. Biol. Chem. 272:24313-24318(1997).
RN [4]
RP TISSUE SPECIFICITY.
RX PubMed=10103025; DOI=10.1046/j.1432-1327.1999.00253.x;
RA Horstkorte R., Noehring S., Wiechens N., Schwarzkopf M., Danker K.,
RA Reutter W., Lucka L.;
RT "Tissue expression and amino acid sequence of murine UDP-N-
RT acetylglucosamine-2-epimerase/N-acetylmannosamine kinase.";
RL Eur. J. Biochem. 260:923-927(1999).
RN [5]
RP MUTAGENESIS OF HIS-49; HIS-110; HIS-132; HIS-155; HIS-157; ASP-413 AND
RP ARG-420.
RX PubMed=10497249; DOI=10.1074/jbc.274.40.28771;
RA Effertz K., Hinderlich S., Reutter W.;
RT "Selective loss of either the epimerase or kinase activity of UDP-N-
RT acetylglucosamine 2-epimerase/N-acetylmannosamine kinase due to site-
RT directed mutagenesis based on sequence alignments.";
RL J. Biol. Chem. 274:28771-28778(1999).
CC -!- FUNCTION: Regulates and initiates biosynthesis of N-acetylneuraminic
CC acid (NeuAc), a precursor of sialic acids. Required for normal
CC sialylation in hematopoietic cells. Sialylation is implicated in cell
CC adhesion, signal transduction, tumorigenicity and metastatic behavior
CC of malignant cells. Plays an essential role in early development (By
CC similarity). {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + UDP-N-acetyl-alpha-D-glucosamine = H(+) + N-acetyl-D-
CC mannosamine + UDP; Xref=Rhea:RHEA:30683, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17122, ChEBI:CHEBI:57705,
CC ChEBI:CHEBI:58223; EC=3.2.1.183;
CC Evidence={ECO:0000269|PubMed:9305887};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an N-acyl-D-mannosamine + ATP = ADP + an N-acyl-D-mannosamine
CC 6-phosphate + H(+); Xref=Rhea:RHEA:23832, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16062, ChEBI:CHEBI:30616, ChEBI:CHEBI:57666,
CC ChEBI:CHEBI:456216; EC=2.7.1.60;
CC Evidence={ECO:0000269|PubMed:9305887};
CC -!- ACTIVITY REGULATION: Allosterically regulated (By similarity); feedback
CC inhibited by cytidine monophosphate-N-acetylneuraminic acid (CMP-
CC Neu5Ac), the end product of neuraminic acid biosynthesis. Activity is
CC dependent on oligomerization. The monomer is inactive, whereas the
CC dimer catalyzes only the phosphorylation of N-acetylmannosamine, and
CC the hexamer is fully active for both enzyme activities. Up-regulated
CC after PKC-dependent phosphorylation. {ECO:0000250,
CC ECO:0000269|PubMed:9305887}.
CC -!- PATHWAY: Amino-sugar metabolism; N-acetylneuraminate biosynthesis.
CC -!- SUBUNIT: Homodimer and homohexamer. {ECO:0000269|PubMed:9305887}.
CC -!- INTERACTION:
CC O35826; Q05516: ZBTB16; Xeno; NbExp=2; IntAct=EBI-7109445, EBI-711925;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:9305887,
CC ECO:0000269|PubMed:9305888}.
CC -!- TISSUE SPECIFICITY: Widely expressed. Highest expression is observed in
CC liver. {ECO:0000269|PubMed:10103025, ECO:0000269|PubMed:9305888}.
CC -!- PTM: Phosphorylated by PKC. {ECO:0000250}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the UDP-N-
CC acetylglucosamine 2-epimerase family. {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the ROK (NagC/XylR)
CC family. {ECO:0000305}.
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DR EMBL; Y07744; CAA69024.1; -; mRNA.
DR EMBL; BC062011; AAH62011.1; -; mRNA.
DR RefSeq; NP_446217.1; NM_053765.2.
DR RefSeq; XP_006238070.1; XM_006238008.1.
DR RefSeq; XP_006238071.1; XM_006238009.3.
DR AlphaFoldDB; O35826; -.
DR SMR; O35826; -.
DR BioGRID; 250408; 6.
DR IntAct; O35826; 5.
DR MINT; O35826; -.
DR STRING; 10116.ENSRNOP00000019532; -.
DR iPTMnet; O35826; -.
DR PhosphoSitePlus; O35826; -.
DR jPOST; O35826; -.
DR PaxDb; O35826; -.
DR PRIDE; O35826; -.
DR Ensembl; ENSRNOT00000019532; ENSRNOP00000019532; ENSRNOG00000014365.
DR GeneID; 114711; -.
DR KEGG; rno:114711; -.
DR UCSC; RGD:69239; rat.
DR CTD; 10020; -.
DR RGD; 69239; Gne.
DR eggNOG; ENOG502QUGI; Eukaryota.
DR GeneTree; ENSGT00390000017246; -.
DR HOGENOM; CLU_023411_0_0_1; -.
DR InParanoid; O35826; -.
DR PhylomeDB; O35826; -.
DR BioCyc; MetaCyc:MON-14506; -.
DR BRENDA; 5.1.3.14; 5301.
DR Reactome; R-RNO-4085001; Sialic acid metabolism.
DR SABIO-RK; O35826; -.
DR UniPathway; UPA00630; -.
DR PRO; PR:O35826; -.
DR Proteomes; UP000002494; Chromosome 5.
DR Bgee; ENSRNOG00000014365; Expressed in colon and 20 other tissues.
DR ExpressionAtlas; O35826; baseline and differential.
DR Genevisible; O35826; RN.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004553; F:hydrolase activity, hydrolyzing O-glycosyl compounds; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0009384; F:N-acylmannosamine kinase activity; IDA:RGD.
DR GO; GO:0008761; F:UDP-N-acetylglucosamine 2-epimerase activity; IDA:RGD.
DR GO; GO:0006045; P:N-acetylglucosamine biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0046380; P:N-acetylneuraminate biosynthetic process; TAS:RGD.
DR GO; GO:0006047; P:UDP-N-acetylglucosamine metabolic process; IEA:InterPro.
DR InterPro; IPR043129; ATPase_NBD.
DR InterPro; IPR000600; ROK.
DR InterPro; IPR020004; UDP-GlcNAc_Epase.
DR InterPro; IPR003331; UDP_GlcNAc_Epimerase_2_dom.
DR PANTHER; PTHR18964; PTHR18964; 1.
DR Pfam; PF02350; Epimerase_2; 1.
DR Pfam; PF00480; ROK; 1.
DR SUPFAM; SSF53067; SSF53067; 1.
DR TIGRFAMs; TIGR03568; NeuC_NnaA; 1.
PE 1: Evidence at protein level;
KW Allosteric enzyme; ATP-binding; Cytoplasm; Direct protein sequencing;
KW Hydrolase; Kinase; Metal-binding; Multifunctional enzyme;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Transferase; Zinc.
FT CHAIN 1..722
FT /note="Bifunctional UDP-N-acetylglucosamine 2-epimerase/N-
FT acetylmannosamine kinase"
FT /id="PRO_0000095718"
FT REGION 1..?
FT /note="UDP-N-acetylglucosamine 2-epimerase"
FT REGION 406..722
FT /note="N-acetylmannosamine kinase"
FT /evidence="ECO:0000250"
FT ACT_SITE 517
FT /evidence="ECO:0000250"
FT BINDING 411..420
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 477
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 489
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 517
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 543..552
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 566
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 569
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 569
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 579
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 581
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 586
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 588
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT MUTAGEN 49
FT /note="H->A: Does not affect kinase activity; almost
FT complete loss of epimerase activity; does not interfere
FT with enzyme oligomerization."
FT /evidence="ECO:0000269|PubMed:10497249"
FT MUTAGEN 110
FT /note="H->A: Does not affect kinase activity; almost
FT complete loss of epimerase activity; partial reduction of
FT the dimerization process."
FT /evidence="ECO:0000269|PubMed:10497249"
FT MUTAGEN 132
FT /note="H->A: Does not affect kinase activity; almost
FT complete loss of epimerase activity; partial reduction of
FT the dimerization process."
FT /evidence="ECO:0000269|PubMed:10497249"
FT MUTAGEN 155
FT /note="H->A: Does not affect kinase activity; almost
FT complete loss of epimerase activity; strong reduction of
FT the dimerization process."
FT /evidence="ECO:0000269|PubMed:10497249"
FT MUTAGEN 157
FT /note="H->A: Does not affect kinase activity; almost
FT complete loss of epimerase activity; strong reduction of
FT the dimerization process."
FT /evidence="ECO:0000269|PubMed:10497249"
FT MUTAGEN 413
FT /note="D->K,N: Does not affect epimerase activity; does not
FT affect feedback inhibition by CMP-Neu5Ac; almost complete
FT loss of kinase activity; does not interfere with
FT oligomerization."
FT /evidence="ECO:0000269|PubMed:10497249"
FT MUTAGEN 420
FT /note="R->M: Does not affect epimerase activity; does not
FT affect feedback inhibition by CMP-Neu5Ac; almost complete
FT loss of kinase activity; does not interfere with
FT oligomerization."
FT /evidence="ECO:0000269|PubMed:10497249"
SQ SEQUENCE 722 AA; 79227 MW; 0DFDC84E833C7984 CRC64;
MEKNGNNRKL RVCVATCNRA DYSKLAPIMF GIKTEPAFFE LDVVVLGSHL IDDYGNTYRM
IEQDDFDINT RLHTIVRGED EAAMVESVGL ALVKLPDVLN RLKPDIMIVH GDRFDALALA
TSAALMNIRI LHIEGGEVSG TIDDSIRHAI TKLAHYHVCC TRSAEQHLIS MCEDHDRILL
AGCPSYDKLL SAKNKDYMSI IRMWLGDDVK CKDYIVALQH PVTTDIKHSI KMFELTLDAL
ISFNKRTLVL FPNIDAGSKE MVRVMRKKGI EHHPNFRAVK HVPFDQFIQL VAHAGCMIGN
SSCGVREVGA FGTPVINLGT RQIGRETGEN VLHVRDADTQ DKILQALHLQ FGKQYPCSKI
YGDGNAVPRI LKFLKSIDLQ EPLQKKFCFP PVKENISQDI DHILETLSAL AVDLGGTNLR
VAIVSMKGEI VKKYTQFNPK TYEERISLIL QMCVEAAAEA VKLNCRILGV GISTGGRVNP
QEGVVLHSTK LIQEWNSVDL RTPLSDTLHL PVWVDNDGNC AAMAERKFGQ GKGQENFVTL
ITGTGIGGGI IHQHELIHGS SFCAAELGHL VVSLDGPDCS CGSHGCIEAY ASGMALQREA
KKLHDEDLLL VEGMSVPKDE AVGALHLIQA AKLGNVKAQS ILRTAGTALG LGVVNILHTM
NPSLVILSGV LASHYIHIVR DVIRQQALSS VQDVDVVVSD LVDPALLGAA SMVLDYTTRR
IH
