GLCNE_CRIGR
ID GLCNE_CRIGR Reviewed; 722 AA.
AC Q7TQ49;
DT 15-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 03-AUG-2022, entry version 87.
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 Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Cricetulus.
OX NCBI_TaxID=10029;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT GLU-135.
RX PubMed=14561743; DOI=10.1074/jbc.m309967200;
RA Hong Y., Stanley P.;
RT "Lec3 Chinese hamster ovary mutants lack UDP-N-acetylglucosamine 2-
RT epimerase activity because of mutations in the epimerase domain of the Gne
RT gene.";
RL J. Biol. Chem. 278:53045-53054(2003).
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 -!- 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 -!- ACTIVITY REGULATION: Allosterically regulated; feedback inhibited by
CC cytidine monophosphate-N-acetylneuraminic acid (CMP-Neu5Ac), the end
CC product of neuraminic acid biosynthesis. Activity is dependent on
CC oligomerization. The monomer is inactive, whereas the dimer catalyzes
CC only the phosphorylation of N-acetylmannosamine, and the hexamer is
CC fully active for both enzyme activities. Up-regulated after PKC-
CC dependent phosphorylation (By similarity). {ECO:0000250}.
CC -!- PATHWAY: Amino-sugar metabolism; N-acetylneuraminate biosynthesis.
CC -!- SUBUNIT: Homodimer and homohexamer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
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; AB107226; BAC78543.1; -; mRNA.
DR RefSeq; NP_001233638.1; NM_001246709.1.
DR AlphaFoldDB; Q7TQ49; -.
DR SMR; Q7TQ49; -.
DR STRING; 10029.NP_001233638.1; -.
DR GeneID; 100689450; -.
DR KEGG; cge:100689450; -.
DR CTD; 10020; -.
DR eggNOG; ENOG502QUGI; Eukaryota.
DR OrthoDB; 225119at2759; -.
DR UniPathway; UPA00630; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
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; IEA:UniProtKB-EC.
DR GO; GO:0006045; P:N-acetylglucosamine biosynthetic process; IEA:UniProtKB-UniPathway.
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 2: Evidence at transcript level;
KW Allosteric enzyme; ATP-binding; Cytoplasm; Hydrolase; Kinase;
KW Metal-binding; Multifunctional enzyme; Nucleotide-binding; Phosphoprotein;
KW Transferase; Zinc.
FT CHAIN 1..722
FT /note="Bifunctional UDP-N-acetylglucosamine 2-epimerase/N-
FT acetylmannosamine kinase"
FT /id="PRO_0000095715"
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 VARIANT 135
FT /note="G -> E (in Lec3 cell glycosylation mutants; loss of
FT epimerase activity)"
FT /evidence="ECO:0000269|PubMed:14561743"
SQ SEQUENCE 722 AA; 79241 MW; 5AC075CA9DAED642 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
QEGIVLHSTK LIQEWNSVDL RTPLSDTLHL PVWVDNDGNC AAMAERKFGQ GKGQENFVTL
ITGTGIGGGI IHQHELIHGS SFCAAELGHL VVSLDGPDCS CGSHGCIEAY ASGMALQREA
KKLHDEDLLL VEGMSVPKDE PVGALHLIQA AKLGNVKAQN ILRTAGTALG LGVVNILHTM
DPSLVILSGV LASHYIHIVK DVIRQQASSS VQDVDVVVSD LVDPALLGAA SMVLDYTTRR
IH
