ID   NAGK_MOUSE              Reviewed;         343 AA.
AC   Q9QZ08;
DT   01-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 3.
DT   27-MAR-2024, entry version 133.
DE   RecName: Full=N-acetyl-D-glucosamine kinase;
DE            Short=N-acetylglucosamine kinase {ECO:0000303|PubMed:10824116};
DE            EC=2.7.1.59 {ECO:0000269|PubMed:10824116};
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:0000269|PubMed:10824116};
GN   Name=Nagk; Synonyms=Gnk;
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], FUNCTION, CATALYTIC ACTIVITY, PATHWAY, TISSUE
RP   SPECIFICITY, AND SUBUNIT.
RX   PubMed=10824116; DOI=10.1046/j.1432-1327.2000.01360.x;
RA   Hinderlich S., Berger M., Schwarzkopf M., Effertz K., Reutter W.;
RT   "Molecular cloning and characterization of murine and human N-
RT   acetylglucosamine kinase.";
RL   Eur. J. Biochem. 267:3301-3308(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-76, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Heart, Kidney, 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).
RN   [4]
RP   PATHWAY.
RX   PubMed=22692205; DOI=10.1074/jbc.m112.363549;
RA   Bergfeld A.K., Pearce O.M., Diaz S.L., Pham T., Varki A.;
RT   "Metabolism of vertebrate amino sugars with N-glycolyl groups: elucidating
RT   the intracellular fate of the non-human sialic acid N-glycolylneuraminic
RT   acid.";
RL   J. Biol. Chem. 287:28865-28881(2012).
RN   [5]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=36002575; DOI=10.1038/s41586-022-05125-x;
RA   Stafford C.A., Gassauer A.M., de Oliveira Mann C.C., Tanzer M.C.,
RA   Fessler E., Wefers B., Nagl D., Kuut G., Sulek K., Vasilopoulou C.,
RA   Schwojer S.J., Wiest A., Pfautsch M.K., Wurst W., Yabal M., Froehlich T.,
RA   Mann M., Gisch N., Jae L.T., Hornung V.;
RT   "Phosphorylation of muramyl peptides by NAGK is required for NOD2
RT   activation.";
RL   Nature 609:590-596(2022).
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:10824116). Also has
CC       N-acetylmannosamine (ManNAc) kinase activity (PubMed:10824116).
CC       Involved in the N-glycolylneuraminic acid (Neu5Gc) degradation pathway
CC       (PubMed:22692205). Also involved in innate immunity by promoting
CC       detection of bacterial peptidoglycan by NOD2: acts by catalyzing
CC       phosphorylation of muramyl dipeptide (MDP), a fragment of bacterial
CC       peptidoglycan, to generate 6-O-phospho-muramyl dipeptide, which acts as
CC       a direct ligand for NOD2 (PubMed:36002575).
CC       {ECO:0000269|PubMed:10824116, ECO:0000269|PubMed:22692205,
CC       ECO:0000269|PubMed:36002575}.
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:10824116};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17418;
CC         Evidence={ECO:0000305|PubMed:10824116};
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:0000269|PubMed:10824116};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25254;
CC         Evidence={ECO:0000269|PubMed:10824116};
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   -!- PATHWAY: Amino-sugar metabolism; N-acetylneuraminate degradation.
CC       {ECO:0000269|PubMed:10824116, ECO:0000269|PubMed:22692205}.
CC   -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:10824116}.
CC   -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:10824116}.
CC   -!- DISRUPTION PHENOTYPE: No visible phenotype in absence of infection
CC       (PubMed:36002575). Macrophages are completely deficient in muramyl
CC       dipeptide (MDP) sensing (PubMed:36002575).
CC       {ECO:0000269|PubMed:36002575}.
CC   -!- SIMILARITY: Belongs to the eukaryotic-type N-acetylglucosamine kinase
CC       family. {ECO:0000305}.
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DR   EMBL; AJ242909; CAB61849.1; -; mRNA.
DR   EMBL; BC004689; AAH04689.1; -; mRNA.
DR   CCDS; CCDS20286.1; -.
DR   RefSeq; NP_062415.1; NM_019542.2.
DR   AlphaFoldDB; Q9QZ08; -.
DR   SMR; Q9QZ08; -.
DR   BioGRID; 207820; 8.
DR   IntAct; Q9QZ08; 2.
DR   STRING; 10090.ENSMUSP00000109482; -.
DR   iPTMnet; Q9QZ08; -.
DR   PhosphoSitePlus; Q9QZ08; -.
DR   REPRODUCTION-2DPAGE; Q9QZ08; -.
DR   EPD; Q9QZ08; -.
DR   jPOST; Q9QZ08; -.
DR   MaxQB; Q9QZ08; -.
DR   PaxDb; 10090-ENSMUSP00000042026; -.
DR   ProteomicsDB; 287431; -.
DR   Pumba; Q9QZ08; -.
DR   Antibodypedia; 31185; 321 antibodies from 27 providers.
DR   DNASU; 56174; -.
DR   Ensembl; ENSMUST00000037376.14; ENSMUSP00000042026.8; ENSMUSG00000034744.14.
DR   GeneID; 56174; -.
DR   KEGG; mmu:56174; -.
DR   UCSC; uc009coh.2; mouse.
DR   AGR; MGI:1860418; -.
DR   CTD; 55577; -.
DR   MGI; MGI:1860418; Nagk.
DR   VEuPathDB; HostDB:ENSMUSG00000034744; -.
DR   eggNOG; KOG1794; Eukaryota.
DR   GeneTree; ENSGT00510000047418; -.
DR   HOGENOM; CLU_016274_0_0_1; -.
DR   InParanoid; Q9QZ08; -.
DR   OMA; IETRYDM; -.
DR   OrthoDB; 3030525at2759; -.
DR   PhylomeDB; Q9QZ08; -.
DR   TreeFam; TF314158; -.
DR   BRENDA; 2.7.1.59; 3474.
DR   Reactome; R-MMU-446210; Synthesis of UDP-N-acetyl-glucosamine.
DR   SABIO-RK; Q9QZ08; -.
DR   UniPathway; UPA00629; -.
DR   BioGRID-ORCS; 56174; 3 hits in 76 CRISPR screens.
DR   ChiTaRS; Nagk; mouse.
DR   PRO; PR:Q9QZ08; -.
DR   Proteomes; UP000000589; Chromosome 6.
DR   RNAct; Q9QZ08; Protein.
DR   Bgee; ENSMUSG00000034744; Expressed in embryonic brain and 266 other cell types or tissues.
DR   ExpressionAtlas; Q9QZ08; baseline and differential.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0160047; F:muramyl dipeptide kinase activity; IDA:UniProtKB.
DR   GO; GO:0045127; F:N-acetylglucosamine kinase activity; IDA:MGI.
DR   GO; GO:0009384; F:N-acylmannosamine kinase activity; IDA:MGI.
DR   GO; GO:0042742; P:defense response to bacterium; ISO:MGI.
DR   GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR   GO; GO:0006044; P:N-acetylglucosamine metabolic process; IDA:MGI.
DR   GO; GO:0019262; P:N-acetylneuraminate catabolic process; TAS:UniProtKB.
DR   GO; GO:0070434; P:positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway; IDA:UniProtKB.
DR   GO; GO:0032495; P:response to muramyl dipeptide; ISO:MGI.
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; Q9QZ08; MM.
PE   1: Evidence at protein level;
KW   Acetylation; ATP-binding; Immunity; Innate immunity; Kinase;
KW   Nucleotide-binding; Phosphoprotein; Reference proteome; Transferase.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UJ70"
FT   CHAIN           2..343
FT                   /note="N-acetyl-D-glucosamine kinase"
FT                   /id="PRO_0000096697"
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:0000250|UniProtKB:Q9UJ70"
FT   MOD_RES         76
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         205
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UJ70"
SQ   SEQUENCE   343 AA;  37268 MW;  A3832E98C9B3228E CRC64;
     MAALYGGVEG GGTRSKVLLL SEDGQILAEA DGLSTNHWLI GTDQCVERIN EMVDRAKQKA
     GVDPLVPLRS LGLSLSGGEQ EDAVRLLIEE LRHRFPNLSE NYLITTDAAG SIATATPDGG
     IVLISGTGSN CRLINPDGSE SGCGGWGHMM GDEGSAYWIA HQAVKIVFDS IDNLEAAPHD
     IGHVKQAMFD YFQVPDRLGI LTHLYRDFDK CKFAGFCQKI AEGAHQGDPL SRYIFRKAGE
     MLGRHVVAVL PEIDPVLFQG ELGLPILCVG SVWKSWELLK EGFLLALTLG REQQAQNSFS
     SFTLMKLRHS SALGGASLGA RHIGYHLPMD YSINAIAFYS YTF
//