ID   NAGK_RAT                Reviewed;         343 AA.
AC   P81799; Q32Q91;
DT   31-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 4.
DT   27-MAR-2024, entry version 115.
DE   RecName: Full=N-acetyl-D-glucosamine kinase;
DE            Short=N-acetylglucosamine kinase;
DE            EC=2.7.1.59 {ECO:0000269|PubMed:9523722};
DE   AltName: Full=GlcNAc kinase;
DE   AltName: Full=Muramyl dipeptide kinase {ECO:0000305};
DE            EC=2.7.1.- {ECO:0000250|UniProtKB:Q9UJ70};
DE   AltName: Full=N-acetyl-D-mannosamine kinase {ECO:0000305};
DE            EC=2.7.1.60 {ECO:0000250|UniProtKB:Q9QZ08};
GN   Name=Nagk;
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 [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   [2]
RP   PROTEIN SEQUENCE OF 2-13; 69-92; 166-178; 198-207; 221-228; 233-235 AND
RP   308-321, ACETYLATION AT ALA-2, ACTIVITY REGULATION, SUBUNIT, FUNCTION, AND
RP   CATALYTIC ACTIVITY.
RC   STRAIN=Wistar; TISSUE=Liver;
RX   PubMed=9523722; DOI=10.1046/j.1432-1327.1998.2520133.x;
RA   Hinderlich S., Noehring S., Weise C., Franke P., Staesche R., Reutter W.;
RT   "Purification and characterization of N-acetylglucosamine kinase from rat
RT   liver. Comparison with UDP-N-acetylglucosamine 2-epimerase/N-
RT   acetylmannosamine kinase.";
RL   Eur. J. Biochem. 252:133-139(1998).
RN   [3]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-76, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22673903; DOI=10.1038/ncomms1871;
RA   Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA   Olsen J.V.;
RT   "Quantitative maps of protein phosphorylation sites across 14 different rat
RT   organs and tissues.";
RL   Nat. Commun. 3:876-876(2012).
CC   -!- FUNCTION: Converts endogenous N-acetylglucosamine (GlcNAc), a major
CC       component of complex carbohydrates, from lysosomal degradation or
CC       nutritional sources into GlcNAc 6-phosphate (PubMed:9523722). Also has
CC       N-acetylmannosamine (ManNAc) kinase activity (By similarity). Involved
CC       in the N-glycolylneuraminic acid (Neu5Gc) degradation pathway (By
CC       similarity). Also involved in innate immunity by promoting detection of
CC       bacterial peptidoglycan by NOD2: acts by catalyzing phosphorylation of
CC       muramyl dipeptide (MDP), a fragment of bacterial peptidoglycan, to
CC       generate 6-O-phospho-muramyl dipeptide, which acts as a direct ligand
CC       for NOD2 (By similarity). {ECO:0000250|UniProtKB:Q9QZ08,
CC       ECO:0000250|UniProtKB:Q9UJ70, ECO:0000269|PubMed:9523722}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + N-acetyl-D-glucosamine = ADP + H(+) + N-acetyl-D-
CC         glucosamine 6-phosphate; Xref=Rhea:RHEA:17417, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:57513, ChEBI:CHEBI:456216,
CC         ChEBI:CHEBI:506227; EC=2.7.1.59;
CC         Evidence={ECO:0000269|PubMed:9523722};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17418;
CC         Evidence={ECO:0000269|PubMed:9523722};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + N-acetyl-D-mannosamine = ADP + H(+) + N-acetyl-D-
CC         mannosamine 6-phosphate; Xref=Rhea:RHEA:25253, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:17122, ChEBI:CHEBI:30616, ChEBI:CHEBI:58557,
CC         ChEBI:CHEBI:456216; EC=2.7.1.60;
CC         Evidence={ECO:0000250|UniProtKB:Q9QZ08};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25254;
CC         Evidence={ECO:0000250|UniProtKB:Q9QZ08};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + N-acetyl-D-muramoyl-L-alanyl-D-isoglutamine = 6-O-
CC         phospho-N-acetyl-D-muramoyl-L-alanyl-D-isoglutamine + ADP + H(+);
CC         Xref=Rhea:RHEA:75935, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:155830, ChEBI:CHEBI:194492, ChEBI:CHEBI:456216;
CC         Evidence={ECO:0000250|UniProtKB:Q9UJ70};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75936;
CC         Evidence={ECO:0000250|UniProtKB:Q9UJ70};
CC   -!- ACTIVITY REGULATION: Inhibited by the cysteine modifiers iodoacetamide,
CC       N-ethylmaleimide and 5,5'-dithiobis(2-nitrobenzoic acid).
CC       {ECO:0000269|PubMed:9523722}.
CC   -!- PATHWAY: Amino-sugar metabolism; N-acetylneuraminate degradation.
CC       {ECO:0000250|UniProtKB:Q9QZ08}.
CC   -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:9523722}.
CC   -!- SIMILARITY: Belongs to the eukaryotic-type N-acetylglucosamine kinase
CC       family. {ECO:0000305}.
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DR   EMBL; BC107647; AAI07648.1; -; mRNA.
DR   RefSeq; NP_001032857.1; NM_001037768.1.
DR   AlphaFoldDB; P81799; -.
DR   SMR; P81799; -.
DR   IntAct; P81799; 1.
DR   STRING; 10116.ENSRNOP00000039247; -.
DR   iPTMnet; P81799; -.
DR   PhosphoSitePlus; P81799; -.
DR   jPOST; P81799; -.
DR   PaxDb; 10116-ENSRNOP00000039247; -.
DR   Ensembl; ENSRNOT00000108444.1; ENSRNOP00000084218.1; ENSRNOG00000013911.7.
DR   Ensembl; ENSRNOT00055020645; ENSRNOP00055016636; ENSRNOG00055012149.
DR   Ensembl; ENSRNOT00060005148; ENSRNOP00060003786; ENSRNOG00060003115.
DR   Ensembl; ENSRNOT00065026839; ENSRNOP00065021083; ENSRNOG00065016128.
DR   GeneID; 297393; -.
DR   KEGG; rno:297393; -.
DR   UCSC; RGD:1305057; rat.
DR   AGR; RGD:1305057; -.
DR   CTD; 55577; -.
DR   RGD; 1305057; Nagk.
DR   eggNOG; KOG1794; Eukaryota.
DR   GeneTree; ENSGT00510000047418; -.
DR   HOGENOM; CLU_016274_0_0_1; -.
DR   InParanoid; P81799; -.
DR   OMA; IETRYDM; -.
DR   OrthoDB; 3030525at2759; -.
DR   PhylomeDB; P81799; -.
DR   TreeFam; TF314158; -.
DR   Reactome; R-RNO-446210; Synthesis of UDP-N-acetyl-glucosamine.
DR   SABIO-RK; P81799; -.
DR   UniPathway; UPA00629; -.
DR   PRO; PR:P81799; -.
DR   Proteomes; UP000002494; Chromosome 4.
DR   Bgee; ENSRNOG00000013911; Expressed in duodenum and 19 other cell types or tissues.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0160047; F:muramyl dipeptide kinase activity; ISS:UniProtKB.
DR   GO; GO:0045127; F:N-acetylglucosamine kinase activity; ISS:UniProtKB.
DR   GO; GO:0009384; F:N-acylmannosamine kinase activity; ISO:RGD.
DR   GO; GO:0046835; P:carbohydrate phosphorylation; ISO:RGD.
DR   GO; GO:0042742; P:defense response to bacterium; ISS:UniProtKB.
DR   GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR   GO; GO:0006044; P:N-acetylglucosamine metabolic process; ISO:RGD.
DR   GO; GO:0019262; P:N-acetylneuraminate catabolic process; IEA:UniProtKB-UniPathway.
DR   GO; GO:0070434; P:positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway; ISS:UniProtKB.
DR   GO; GO:0032495; P:response to muramyl dipeptide; ISS:UniProtKB.
DR   CDD; cd00012; NBD_sugar-kinase_HSP70_actin; 1.
DR   Gene3D; 3.30.420.40; -; 1.
DR   InterPro; IPR002731; ATPase_BadF.
DR   InterPro; IPR043129; ATPase_NBD.
DR   InterPro; IPR039758; NAGK_prok_euk.
DR   PANTHER; PTHR12862; BADF TYPE ATPASE DOMAIN-CONTAINING PROTEIN; 1.
DR   PANTHER; PTHR12862:SF0; N-ACETYL-D-GLUCOSAMINE KINASE; 1.
DR   Pfam; PF01869; BcrAD_BadFG; 1.
DR   SUPFAM; SSF53067; Actin-like ATPase domain; 2.
DR   Genevisible; P81799; RN.
PE   1: Evidence at protein level;
KW   Acetylation; ATP-binding; Direct protein sequencing; Immunity;
KW   Innate immunity; Kinase; Nucleotide-binding; Phosphoprotein;
KW   Reference proteome; Transferase.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000269|PubMed:9523722"
FT   CHAIN           2..343
FT                   /note="N-acetyl-D-glucosamine kinase"
FT                   /id="PRO_0000096698"
FT   BINDING         13
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UJ70"
FT   BINDING         36
FT                   /ligand="N-acetyl-D-glucosamine"
FT                   /ligand_id="ChEBI:CHEBI:506227"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UJ70"
FT   BINDING         107
FT                   /ligand="N-acetyl-D-glucosamine"
FT                   /ligand_id="ChEBI:CHEBI:506227"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UJ70"
FT   BINDING         127
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UJ70"
FT   BINDING         129..130
FT                   /ligand="N-acetyl-D-glucosamine"
FT                   /ligand_id="ChEBI:CHEBI:506227"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UJ70"
FT   BINDING         145..147
FT                   /ligand="N-acetyl-D-glucosamine"
FT                   /ligand_id="ChEBI:CHEBI:506227"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UJ70"
FT   BINDING         152
FT                   /ligand="N-acetyl-D-glucosamine"
FT                   /ligand_id="ChEBI:CHEBI:506227"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UJ70"
FT   BINDING         214
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UJ70"
FT   BINDING         271
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UJ70"
FT   BINDING         275
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UJ70"
FT   MOD_RES         2
FT                   /note="N-acetylalanine"
FT                   /evidence="ECO:0000269|PubMed:9523722"
FT   MOD_RES         76
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         205
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UJ70"
FT   CONFLICT        207
FT                   /note="D -> T (in Ref. 2; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        226
FT                   /note="Q -> E (in Ref. 2; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        309
FT                   /note="H -> I (in Ref. 2; AA sequence)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   343 AA;  37196 MW;  43886E3262D08A0F CRC64;
     MAALYGGVEG GGTRSKVLLL SEDGQILAEA DGLSTNHWLI GTGTCVERIN EMVDRAKRKA
     GVDPLVPLRS LGLSLSGGEQ EDAVRLLMEE LRDRFPYLSE SYFITTDAAG SIATATPDGG
     IVLISGTGSN CRLINPDGSE SGCGGWGHMM GDEGSAYWIA HQAVKIVFDS IDNLEAAPHD
     IGHVKQAMFN YFQVPDRLGI LTHLYRDFDK SKFAGFCQKI AEGAQQGDPL SRFIFRKAGE
     MLGRHVVAVL PEIDPVLFQG ELGLPILCVG SVWKSWELLK EGFLLALTQG REQQAQNSFS
     SFTLMKLRHS SALGGASLGA RHIGHHLPMD YSVNAIAFYS YTF
//