ID HXK1_CANAL Reviewed; 493 AA. AC Q59RW5; A0A1D8PQG2; Q59RG5; DT 04-FEB-2015, integrated into UniProtKB/Swiss-Prot. DT 15-MAR-2017, sequence version 2. DT 27-MAR-2024, entry version 107. DE RecName: Full=N-acetylglucosamine kinase 1 {ECO:0000303|PubMed:11114181}; DE Short=GlcNAc kinase 1 {ECO:0000305}; DE EC=2.7.1.59 {ECO:0000269|PubMed:11298769}; DE AltName: Full=Hexokinase 1 {ECO:0000305}; DE EC=2.7.1.1 {ECO:0000269|PubMed:11298769}; GN Name=HXK1 {ECO:0000303|PubMed:11114181}; GN Synonyms=NAG5 {ECO:0000303|PubMed:11298769}; GN OrderedLocusNames=CAALFM_C604580WA; ORFNames=CaO19.2154, CaO19.9701; OS Candida albicans (strain SC5314 / ATCC MYA-2876) (Yeast). OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes; OC Saccharomycetales; Debaryomycetaceae; Candida/Lodderomyces clade; Candida. OX NCBI_TaxID=237561; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=SC5314 / ATCC MYA-2876; RX PubMed=15123810; DOI=10.1073/pnas.0401648101; RA Jones T., Federspiel N.A., Chibana H., Dungan J., Kalman S., Magee B.B., RA Newport G., Thorstenson Y.R., Agabian N., Magee P.T., Davis R.W., RA Scherer S.; RT "The diploid genome sequence of Candida albicans."; RL Proc. Natl. Acad. Sci. U.S.A. 101:7329-7334(2004). RN [2] RP GENOME REANNOTATION. RC STRAIN=SC5314 / ATCC MYA-2876; RX PubMed=17419877; DOI=10.1186/gb-2007-8-4-r52; RA van het Hoog M., Rast T.J., Martchenko M., Grindle S., Dignard D., RA Hogues H., Cuomo C., Berriman M., Scherer S., Magee B.B., Whiteway M., RA Chibana H., Nantel A., Magee P.T.; RT "Assembly of the Candida albicans genome into sixteen supercontigs aligned RT on the eight chromosomes."; RL Genome Biol. 8:RESEARCH52.1-RESEARCH52.12(2007). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND GENOME REANNOTATION. RC STRAIN=SC5314 / ATCC MYA-2876; RX PubMed=24025428; DOI=10.1186/gb-2013-14-9-r97; RA Muzzey D., Schwartz K., Weissman J.S., Sherlock G.; RT "Assembly of a phased diploid Candida albicans genome facilitates allele- RT specific measurements and provides a simple model for repeat and indel RT structure."; RL Genome Biol. 14:RESEARCH97.1-RESEARCH97.14(2013). RN [4] RP IDENTIFICATION, AND INDUCTION. RX PubMed=11114181; DOI=10.1073/pnas.250452997; RA Kumar M.J., Jamaluddin M.S., Natarajan K., Kaur D., Datta A.; RT "The inducible N-acetylglucosamine catabolic pathway gene cluster in RT Candida albicans: discrete N-acetylglucosamine-inducible factors interact RT at the promoter of NAG1."; RL Proc. Natl. Acad. Sci. U.S.A. 97:14218-14223(2000). RN [5] RP IDENTIFICATION, DISRUPTION PHENOTYPE, FUNCTION, CATALYTIC ACTIVITY, AND RP BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=11298769; DOI=10.1046/j.1432-1327.2001.02135.x; RA Yamada-Okabe T., Sakamori Y., Mio T., Yamada-Okabe H.; RT "Identification and characterization of the genes for N-acetylglucosamine RT kinase and N-acetylglucosamine-phosphate deacetylase in the pathogenic RT fungus Candida albicans."; RL Eur. J. Biochem. 268:2498-2505(2001). RN [6] RP DISRUPTION PHENOTYPE, AND FUNCTION. RX PubMed=11705974; DOI=10.1128/iai.69.12.7898-7903.2001; RA Singh P., Ghosh S., Datta A.; RT "Attenuation of virulence and changes in morphology in Candida albicans by RT disruption of the N-acetylglucosamine catabolic pathway."; RL Infect. Immun. 69:7898-7903(2001). RN [7] RP DISRUPTION PHENOTYPE, AND FUNCTION. RX PubMed=17139615; DOI=10.1002/jobm.200610167; RA Wendland J., Hellwig D., Walther A., Sickinger S., Shadkchan Y., Martin R., RA Bauer J., Osherov N., Tretiakov A., Saluz H.P.; RT "Use of the porcine intestinal epithelium (PIE)-assay to analyze early RT stages of colonization by the human fungal pathogen Candida albicans."; RL J. Basic Microbiol. 46:513-523(2006). RN [8] RP INDUCTION. RX PubMed=16987174; DOI=10.1111/j.1365-2958.2006.05367.x; RA Bennett R.J., Johnson A.D.; RT "The role of nutrient regulation and the Gpa2 protein in the mating RT pheromone response of C. albicans."; RL Mol. Microbiol. 62:100-119(2006). RN [9] RP FUNCTION. RX PubMed=19648376; DOI=10.1128/aem.00053-09; RA Wendland J., Schaub Y., Walther A.; RT "N-acetylglucosamine utilization by Saccharomyces cerevisiae based on RT expression of Candida albicans NAG genes."; RL Appl. Environ. Microbiol. 75:5840-5845(2009). RN [10] RP INDUCTION. RX PubMed=20675577; DOI=10.1128/ec.00178-10; RA Gunasekera A., Alvarez F.J., Douglas L.M., Wang H.X., Rosebrock A.P., RA Konopka J.B.; RT "Identification of GIG1, a GlcNAc-induced gene in Candida albicans needed RT for normal sensitivity to the chitin synthase inhibitor nikkomycin Z."; RL Eukaryot. Cell 9:1476-1483(2010). RN [11] RP DISRUPTION PHENOTYPE, AND FUNCTION. RX PubMed=21700702; DOI=10.1074/jbc.m111.249854; RA Naseem S., Gunasekera A., Araya E., Konopka J.B.; RT "N-acetylglucosamine (GlcNAc) induction of hyphal morphogenesis and RT transcriptional responses in Candida albicans are not dependent on its RT metabolism."; RL J. Biol. Chem. 286:28671-28680(2011). RN [12] RP DISRUPTION PHENOTYPE, INDUCTION, INTERACTION WITH SIR2, FUNCTION, AND RP SUBCELLULAR LOCATION. RX PubMed=23341961; DOI=10.1371/journal.pone.0053638; RA Rao K.H., Ghosh S., Natarajan K., Datta A.; RT "N-acetylglucosamine kinase, HXK1 is involved in morphogenetic transition RT and metabolic gene expression in Candida albicans."; RL PLoS ONE 8:E53638-E53638(2013). RN [13] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=24491547; DOI=10.1016/j.bbrc.2014.01.123; RA Rao K.H., Ruhela D., Ghosh S., Abdin M.Z., Datta A.; RT "N-acetylglucosamine kinase, HXK1 contributes to white-opaque morphological RT transition in Candida albicans."; RL Biochem. Biophys. Res. Commun. 445:138-144(2014). CC -!- FUNCTION: Component of the N-acetylglucosamine catabolic cascade that CC phosphorylates N-acetylglucosamine (GlcNAc), and allows the unique CC ability to utilise GlcNAc as carbon source. Converts GlcNAc to GlcNAc- CC 6-P. Also able to phosphorylate glucose, glucosamine (GlcN), and CC mannose. Galactose, fructose, N-acetylmannosamine (ManNAc), mannosamine CC (ManN), galactosamine (GalN), and N-acetylgalactosamine (GalNAc) are CC not phosphorylated by HXK1. GlcNAc metabolism is closely associated CC with virulence and morphogenesis, and is involved in the cell wall CC synthesis. Acts both as a repressor and an activator of genes involved CC in maintaining cellular homeostasis. Contributes to white-opaque CC morphological transition and plays a role as a filamentation repressor. CC {ECO:0000269|PubMed:11298769, ECO:0000269|PubMed:11705974, CC ECO:0000269|PubMed:17139615, ECO:0000269|PubMed:19648376, CC ECO:0000269|PubMed:21700702, ECO:0000269|PubMed:23341961, CC ECO:0000269|PubMed:24491547}. 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:11298769}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17418; CC Evidence={ECO:0000269|PubMed:11298769}; CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + D-mannose = ADP + D-mannose 6-phosphate + H(+); CC Xref=Rhea:RHEA:11028, ChEBI:CHEBI:4208, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:58735, ChEBI:CHEBI:456216; EC=2.7.1.1; CC Evidence={ECO:0000269|PubMed:11298769}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11029; CC Evidence={ECO:0000269|PubMed:11298769}; CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + D-glucose = ADP + D-glucose 6-phosphate + H(+); CC Xref=Rhea:RHEA:17825, ChEBI:CHEBI:4167, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61548, ChEBI:CHEBI:456216; EC=2.7.1.1; CC Evidence={ECO:0000269|PubMed:11298769}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17826; CC Evidence={ECO:0000269|PubMed:11298769}; CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + D-glucosamine = ADP + D-glucosamine 6-phosphate + H(+); CC Xref=Rhea:RHEA:10948, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:58723, ChEBI:CHEBI:58725, ChEBI:CHEBI:456216; EC=2.7.1.1; CC Evidence={ECO:0000269|PubMed:11298769}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10949; CC Evidence={ECO:0000269|PubMed:11298769}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=375.5 uM for N-acetylglucosamine (GlcNAc) CC {ECO:0000269|PubMed:11298769}; CC KM=482.5 uM for glucose {ECO:0000269|PubMed:11298769}; CC KM=426 uM for mannose {ECO:0000269|PubMed:11298769}; CC -!- PATHWAY: Carbohydrate metabolism; hexose metabolism. CC {ECO:0000305|PubMed:11298769}. CC -!- PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3- CC phosphate and glycerone phosphate from D-glucose: step 1/4. CC {ECO:0000305|PubMed:11298769}. CC -!- SUBUNIT: Interacts with histone deacetylase SIR2 under filamentation- CC inducing conditions. {ECO:0000269|PubMed:23341961}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:23341961}. Nucleus CC {ECO:0000269|PubMed:23341961}. Mitochondrion CC {ECO:0000269|PubMed:23341961}. Note=Localized in cytoplasm and nucleus CC in a filamentation-inducing medium whereas in 2% GlcNAc, where CC catabolism is more prominent, a major fraction is seen to be present in CC cytoplasm. Localizes to mitochondria in non-fermentative carbon sources CC like ethanol. {ECO:0000269|PubMed:23341961}. CC -!- INDUCTION: Expression is induced by N-acetylglucosamine (GlcNAc), by CC the alpha pheromone, and in filamentation-inducing media. CC {ECO:0000269|PubMed:11114181, ECO:0000269|PubMed:16987174, CC ECO:0000269|PubMed:20675577, ECO:0000269|PubMed:23341961}. CC -!- DISRUPTION PHENOTYPE: Greatly retards the growth of cells using GlcNAc CC as the sole carbon source, increases resistance against farnesol, and CC attenuates the virulence in a mouse systemic infection model. Leads to CC derepression of opaque specific gene expression, as well as to CC constitutive filamentous growth and hyperfilamentation in CC filamentation-inducing conditions. {ECO:0000269|PubMed:11298769, CC ECO:0000269|PubMed:11705974, ECO:0000269|PubMed:17139615, CC ECO:0000269|PubMed:21700702, ECO:0000269|PubMed:23341961, CC ECO:0000269|PubMed:24491547}. CC -!- SIMILARITY: Belongs to the hexokinase family. {ECO:0000255|PROSITE- CC ProRule:PRU01084, 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; CP017628; AOW30374.1; -; Genomic_DNA. DR RefSeq; XP_712429.2; XM_707336.2. DR AlphaFoldDB; Q59RW5; -. DR SASBDB; Q59RW5; -. DR SMR; Q59RW5; -. DR STRING; 237561.Q59RW5; -. DR EnsemblFungi; C6_04580W_A-T; C6_04580W_A-T-p1; C6_04580W_A. DR GeneID; 3645964; -. DR KEGG; cal:CAALFM_C604580WA; -. DR CGD; CAL0000186127; HXK1. DR VEuPathDB; FungiDB:C6_04580W_A; -. DR eggNOG; KOG1369; Eukaryota. DR HOGENOM; CLU_014393_4_1_1; -. DR InParanoid; Q59RW5; -. DR OrthoDB; 5481886at2759; -. DR BRENDA; 2.7.1.59; 1096. DR SABIO-RK; Q59RW5; -. DR UniPathway; UPA00109; UER00180. DR UniPathway; UPA00242; -. DR PHI-base; PHI:10642; -. DR PHI-base; PHI:217; -. DR PRO; PR:Q59RW5; -. DR Proteomes; UP000000559; Chromosome 6. DR GO; GO:0005829; C:cytosol; IDA:CGD. DR GO; GO:0005739; C:mitochondrion; IDA:CGD. DR GO; GO:0005634; C:nucleus; IDA:CGD. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0008865; F:fructokinase activity; IBA:GO_Central. DR GO; GO:0004340; F:glucokinase activity; IBA:GO_Central. DR GO; GO:0047931; F:glucosamine kinase activity; IEA:RHEA. DR GO; GO:0005536; F:glucose binding; IEA:InterPro. DR GO; GO:0019158; F:mannokinase activity; IBA:GO_Central. DR GO; GO:0045127; F:N-acetylglucosamine kinase activity; IDA:CGD. DR GO; GO:0044406; P:adhesion of symbiont to host; IDA:CGD. DR GO; GO:0051701; P:biological process involved in interaction with host; IMP:CGD. DR GO; GO:0046835; P:carbohydrate phosphorylation; IBA:GO_Central. DR GO; GO:0071555; P:cell wall organization; IEA:UniProtKB-KW. DR GO; GO:0044114; P:development of symbiont in host; IMP:CGD. DR GO; GO:0030447; P:filamentous growth; IMP:CGD. DR GO; GO:0044182; P:filamentous growth of a population of unicellular organisms; IMP:CGD. DR GO; GO:0006043; P:glucosamine catabolic process; IMP:CGD. DR GO; GO:0051156; P:glucose 6-phosphate metabolic process; IBA:GO_Central. DR GO; GO:0006006; P:glucose metabolic process; IBA:GO_Central. DR GO; GO:0006096; P:glycolytic process; IBA:GO_Central. DR GO; GO:0001678; P:intracellular glucose homeostasis; IBA:GO_Central. DR GO; GO:0006013; P:mannose metabolic process; IBA:GO_Central. DR GO; GO:0006046; P:N-acetylglucosamine catabolic process; IMP:CGD. DR GO; GO:1900239; P:regulation of phenotypic switching; IMP:CGD. DR Gene3D; 3.30.420.40; -; 1. DR Gene3D; 3.40.367.20; -; 1. DR InterPro; IPR043129; ATPase_NBD. DR InterPro; IPR001312; Hexokinase. DR InterPro; IPR022673; Hexokinase_C. DR InterPro; IPR022672; Hexokinase_N. DR PANTHER; PTHR19443; HEXOKINASE; 1. DR PANTHER; PTHR19443:SF24; HEXOKINASE YLR446W-RELATED; 1. DR Pfam; PF00349; Hexokinase_1; 1. DR Pfam; PF03727; Hexokinase_2; 1. DR PRINTS; PR00475; HEXOKINASE. DR SUPFAM; SSF53067; Actin-like ATPase domain; 2. DR PROSITE; PS51748; HEXOKINASE_2; 1. PE 1: Evidence at protein level; KW ATP-binding; Cell wall biogenesis/degradation; Cytoplasm; Glycolysis; KW Kinase; Mitochondrion; Nucleotide-binding; Nucleus; Reference proteome; KW Transferase; Virulence. FT CHAIN 1..493 FT /note="N-acetylglucosamine kinase 1" FT /id="PRO_0000431722" FT DOMAIN 27..490 FT /note="Hexokinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084" FT REGION 79..221 FT /note="Hexokinase small subdomain" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084" FT REGION 222..479 FT /note="Hexokinase large subdomain" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084" SQ SEQUENCE 493 AA; 54823 MW; F1C4A571B9552FC5 CRC64; MTETSISGLR GPKSMYFMEI VDVSSQESSV LSSIVESFTS AVSASNLGVY SDEVLCDIKS SLKENSPITM LPNYNVSPTG DEHGQYLVID LGGSTLRIAV VDISKPHPNL SRSERITIVV EKSWIIGNDF KRIDGEFFKY IGSKINEILM GQNVIDVKSV INTGITWSFP LETTDYNRGK IKHVSKGYTV GEDIYDKDLK MVLEDTLRQE YGLTLDVQSI LNDSLAVYSA GCFIDSKMKL AMVLGTGINM CCSLKRSSDI HPSKMLADAT LFNCELSLFG QNLCKDFATK YDIIIDKRFA GLSHHFKTFM EPDPITKTLF QPHELMTSGR YLPELTRLVV VDLIEAGEIF QNVDHQQMYQ EYGGFSGELI CFVHENDDYD DIHDKLCKAY GWTTVGLSDI VCLKEVVSCI IKRAAFIVAN AIIAFFKLLG SDELGGDVTI GYVGSVLNYF HKYRRLIVEY VNSAEEAKGI KVDLKLIENS SIIGAAIGAA YHK //