GLCNE_MOUSE
ID GLCNE_MOUSE Reviewed; 722 AA.
AC Q91WG8; Q8CC83; Q8CCB0; Q9Z0P6;
DT 15-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 148.
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, Uae1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC STRAIN=BALB/cJ; TISSUE=Liver;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Colon;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 572-722.
RC STRAIN=C57BL/6J; TISSUE=Colon;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP PHOSPHORYLATION.
RX PubMed=10745088; DOI=10.1016/s0014-5793(00)01331-4;
RA Horstkorte R., Noehring S., Danker K., Effertz K., Reutter W., Lucka L.;
RT "Protein kinase C phosphorylates and regulates UDP-N-acetylglucosamine-2-
RT epimerase/N-acetylmannosamine kinase.";
RL FEBS Lett. 470:315-318(2000).
RN [5]
RP FUNCTION.
RX PubMed=11929971; DOI=10.1073/pnas.072066199;
RA Schwarzkopf M., Knobeloch K.-P., Rohde E., Hinderlich S., Wiechens N.,
RA Lucka L., Horak I., Reutter W., Horstkorte R.;
RT "Sialylation is essential for early development in mice.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:5267-5270(2002).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Liver, Lung, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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 (By similarity). Sialylation is
CC implicated in cell adhesion, signal transduction, tumorigenicity and
CC metastatic behavior of malignant cells. Plays an essential role in
CC early development. {ECO:0000250, ECO:0000269|PubMed:11929971}.
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; the hexamer is fully
CC active for both enzyme activities (By similarity). Up-regulated after
CC PKC-dependent phosphorylation. {ECO:0000250}.
CC -!- PATHWAY: Amino-sugar metabolism; N-acetylneuraminate biosynthesis.
CC -!- SUBUNIT: Homodimer and homohexamer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Widely expressed. Highest expression in liver. Also
CC found at high levels in lung, brain and kidney.
CC {ECO:0000269|PubMed:10103025}.
CC -!- DEVELOPMENTAL STAGE: In the embryo, expressed at day 7 dpc, 11 dpc and
CC 15 dpc. {ECO:0000269|PubMed:10103025}.
CC -!- PTM: Phosphorylated by PKC. {ECO:0000269|PubMed:10745088}.
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AJ132236; CAB36908.1; -; mRNA.
DR EMBL; BC015277; AAH15277.1; -; mRNA.
DR EMBL; BC051254; AAH51254.1; -; mRNA.
DR EMBL; AK033507; BAC28328.1; -; mRNA.
DR EMBL; AK033691; BAC28432.1; -; mRNA.
DR CCDS; CCDS51170.1; -.
DR RefSeq; NP_001177343.1; NM_001190414.1.
DR RefSeq; NP_056643.3; NM_015828.3.
DR AlphaFoldDB; Q91WG8; -.
DR SMR; Q91WG8; -.
DR STRING; 10090.ENSMUSP00000030201; -.
DR iPTMnet; Q91WG8; -.
DR PhosphoSitePlus; Q91WG8; -.
DR SwissPalm; Q91WG8; -.
DR EPD; Q91WG8; -.
DR jPOST; Q91WG8; -.
DR MaxQB; Q91WG8; -.
DR PaxDb; Q91WG8; -.
DR PRIDE; Q91WG8; -.
DR ProteomicsDB; 267633; -.
DR Antibodypedia; 2058; 248 antibodies from 27 providers.
DR DNASU; 50798; -.
DR Ensembl; ENSMUST00000102936; ENSMUSP00000100000; ENSMUSG00000028479.
DR GeneID; 50798; -.
DR KEGG; mmu:50798; -.
DR UCSC; uc008srm.2; mouse.
DR CTD; 10020; -.
DR MGI; MGI:1354951; Gne.
DR VEuPathDB; HostDB:ENSMUSG00000028479; -.
DR eggNOG; ENOG502QUGI; Eukaryota.
DR GeneTree; ENSGT00390000017246; -.
DR InParanoid; Q91WG8; -.
DR OMA; HELYFKK; -.
DR OrthoDB; 225119at2759; -.
DR BRENDA; 2.7.1.60; 3474.
DR BRENDA; 3.2.1.183; 3474.
DR Reactome; R-MMU-4085001; Sialic acid metabolism.
DR UniPathway; UPA00630; -.
DR BioGRID-ORCS; 50798; 12 hits in 78 CRISPR screens.
DR ChiTaRS; Gne; mouse.
DR PRO; PR:Q91WG8; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q91WG8; protein.
DR Bgee; ENSMUSG00000028479; Expressed in submandibular gland and 261 other tissues.
DR ExpressionAtlas; Q91WG8; baseline and differential.
DR Genevisible; Q91WG8; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003824; F:catalytic activity; ISS:MGI.
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; ISO:MGI.
DR GO; GO:0008761; F:UDP-N-acetylglucosamine 2-epimerase activity; ISO:MGI.
DR GO; GO:0006045; P:N-acetylglucosamine biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006054; P:N-acetylneuraminate metabolic process; TAS:MGI.
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; Hydrolase; Kinase;
KW Metal-binding; Multifunctional enzyme; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Transferase; Zinc.
FT CHAIN 1..722
FT /note="Bifunctional UDP-N-acetylglucosamine 2-epimerase/N-
FT acetylmannosamine kinase"
FT /id="PRO_0000095717"
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 CONFLICT 566..567
FT /note="EL -> DV (in Ref. 1; CAB36908)"
FT /evidence="ECO:0000305"
FT CONFLICT 623
FT /note="G -> V (in Ref. 1; CAB36908)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 722 AA; 79199 MW; 0DFDD681BFD17984 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 LASHYIHIVK DVIRQQALSS VQDVDVVVSD LVDPALLGAA SMVLDYTTRR
IH
