HXK1_CANAL
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 03-AUG-2022, entry version 100.
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=426.0 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}.
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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 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 OrthoDB; 1153545at2759; -.
DR BRENDA; 2.7.1.59; 1096.
DR SABIO-RK; Q59RW5; -.
DR UniPathway; UPA00109; UER00180.
DR UniPathway; UPA00242; -.
DR PHI-base; PHI:217; -.
DR PRO; PR:Q59RW5; -.
DR Proteomes; UP000000559; Chromosome 6.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
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; IEA:RHEA.
DR GO; GO:0045127; F:N-acetylglucosamine kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0046835; P:carbohydrate phosphorylation; IBA:GO_Central.
DR GO; GO:0071555; P:cell wall organization; IEA:UniProtKB-KW.
DR GO; GO:0001678; P:cellular glucose homeostasis; IBA:GO_Central.
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 InterPro; IPR043129; ATPase_NBD.
DR InterPro; IPR001312; Hexokinase.
DR InterPro; IPR022673; Hexokinase_C.
DR InterPro; IPR022672; Hexokinase_N.
DR PANTHER; PTHR19443; PTHR19443; 1.
DR Pfam; PF00349; Hexokinase_1; 1.
DR Pfam; PF03727; Hexokinase_2; 1.
DR SUPFAM; SSF53067; SSF53067; 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
