HXK_KLULA
ID HXK_KLULA Reviewed; 485 AA.
AC P33284;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Hexokinase;
DE EC=2.7.1.1 {ECO:0000269|PubMed:12882981};
GN Name=RAG5; OrderedLocusNames=KLLA0D11352g;
OS Kluyveromyces lactis (strain ATCC 8585 / CBS 2359 / DSM 70799 / NBRC 1267 /
OS NRRL Y-1140 / WM37) (Yeast) (Candida sphaerica).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Kluyveromyces.
OX NCBI_TaxID=284590;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 76492 / CBS 2359/152 / CLIB 210, and PM6-7A;
RX PubMed=8321195; DOI=10.1128/mcb.13.7.3882-3889.1993;
RA Prior C., Mamessier P., Fukuhara H., Chen X.J., Wesolowski-Louvel M.;
RT "The hexokinase gene is required for transcriptional regulation of the
RT glucose transporter gene RAG1 in Kluyveromyces lactis.";
RL Mol. Cell. Biol. 13:3882-3889(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 8585 / CBS 2359 / DSM 70799 / NBRC 1267 / NRRL Y-1140 / WM37;
RX PubMed=15229592; DOI=10.1038/nature02579;
RA Dujon B., Sherman D., Fischer G., Durrens P., Casaregola S., Lafontaine I.,
RA de Montigny J., Marck C., Neuveglise C., Talla E., Goffard N., Frangeul L.,
RA Aigle M., Anthouard V., Babour A., Barbe V., Barnay S., Blanchin S.,
RA Beckerich J.-M., Beyne E., Bleykasten C., Boisrame A., Boyer J.,
RA Cattolico L., Confanioleri F., de Daruvar A., Despons L., Fabre E.,
RA Fairhead C., Ferry-Dumazet H., Groppi A., Hantraye F., Hennequin C.,
RA Jauniaux N., Joyet P., Kachouri R., Kerrest A., Koszul R., Lemaire M.,
RA Lesur I., Ma L., Muller H., Nicaud J.-M., Nikolski M., Oztas S.,
RA Ozier-Kalogeropoulos O., Pellenz S., Potier S., Richard G.-F.,
RA Straub M.-L., Suleau A., Swennen D., Tekaia F., Wesolowski-Louvel M.,
RA Westhof E., Wirth B., Zeniou-Meyer M., Zivanovic Y., Bolotin-Fukuhara M.,
RA Thierry A., Bouchier C., Caudron B., Scarpelli C., Gaillardin C.,
RA Weissenbach J., Wincker P., Souciet J.-L.;
RT "Genome evolution in yeasts.";
RL Nature 430:35-44(2004).
RN [3]
RP PROTEIN SEQUENCE OF 2-21; 136-163 AND 198-226, MASS SPECTROMETRY, FUNCTION,
RP CATALYTIC ACTIVITY, SUBUNIT, AND PHOSPHORYLATION AT SER-15.
RC STRAIN=ATCC 76492 / CBS 2359/152 / CLIB 210;
RX PubMed=12882981; DOI=10.1074/jbc.m305706200;
RA Baer D., Golbik R., Huebner G., Lilie H., Mueller E.-C., Naumann M.,
RA Otto A., Reuter R., Breunig K.D., Kriegel T.M.;
RT "The unique hexokinase of Kluyveromyces lactis. Molecular and functional
RT characterization and evaluation of a role in glucose signaling.";
RL J. Biol. Chem. 278:39280-39286(2003).
CC -!- FUNCTION: Catalyzes the phosphorylation of hexose, such as D-glucose
CC and D-fructose, to hexose 6-phosphate (D-glucose 6-phosphate and D-
CC fructose 6-phosphate, respectively) (PubMed:12882981). Has higher
CC affinity for D-glucose (PubMed:12882981). Mediates the initial step of
CC glycolysis by catalyzing phosphorylation of D-glucose to D-glucose 6-
CC phosphate (PubMed:12882981). {ECO:0000269|PubMed:12882981}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + D-hexose = ADP + D-hexose 6-phosphate + H(+);
CC Xref=Rhea:RHEA:22740, ChEBI:CHEBI:4194, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61567, ChEBI:CHEBI:456216; EC=2.7.1.1;
CC Evidence={ECO:0000269|PubMed:12882981};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22741;
CC Evidence={ECO:0000269|PubMed:12882981};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + D-fructose = ADP + D-fructose 6-phosphate + H(+);
CC Xref=Rhea:RHEA:16125, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:37721, ChEBI:CHEBI:61527, ChEBI:CHEBI:456216; EC=2.7.1.1;
CC Evidence={ECO:0000269|PubMed:12882981};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16126;
CC Evidence={ECO:0000269|PubMed:12882981};
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:12882981};
CC -!- PATHWAY: Carbohydrate metabolism; hexose metabolism.
CC {ECO:0000305|PubMed:12882981}.
CC -!- PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-
CC phosphate and glycerone phosphate from D-glucose: step 1/4.
CC {ECO:0000305|PubMed:12882981}.
CC -!- SUBUNIT: Monomer and homodimer. The monomeric form is active, the
CC homodimeric form inactive. {ECO:0000269|PubMed:12882981}.
CC -!- MASS SPECTROMETRY: Mass=53476; Mass_error=5; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:12882981};
CC -!- SIMILARITY: Belongs to the hexokinase family. {ECO:0000255|PROSITE-
CC ProRule:PRU01084, ECO:0000305}.
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DR EMBL; X61680; CAA43855.1; -; Genomic_DNA.
DR EMBL; CR382124; CAH00663.1; -; Genomic_DNA.
DR PIR; A48132; A48132.
DR RefSeq; XP_453567.1; XM_453567.1.
DR PDB; 3O08; X-ray; 2.00 A; A/B=1-485.
DR PDB; 3O1B; X-ray; 2.80 A; A=1-485.
DR PDB; 3O1W; X-ray; 1.66 A; A/B=1-485.
DR PDB; 3O4W; X-ray; 1.61 A; A/B=1-485.
DR PDB; 3O5B; X-ray; 1.97 A; A/B=1-485.
DR PDB; 3O6W; X-ray; 1.48 A; A/B=1-485.
DR PDB; 3O80; X-ray; 2.18 A; A=1-485.
DR PDB; 3O8M; X-ray; 1.42 A; A=1-485.
DR PDB; 4JAX; X-ray; 2.26 A; A/B/C/D/E/F=1-485.
DR PDBsum; 3O08; -.
DR PDBsum; 3O1B; -.
DR PDBsum; 3O1W; -.
DR PDBsum; 3O4W; -.
DR PDBsum; 3O5B; -.
DR PDBsum; 3O6W; -.
DR PDBsum; 3O80; -.
DR PDBsum; 3O8M; -.
DR PDBsum; 4JAX; -.
DR AlphaFoldDB; P33284; -.
DR SMR; P33284; -.
DR STRING; 28985.XP_453567.1; -.
DR iPTMnet; P33284; -.
DR PRIDE; P33284; -.
DR EnsemblFungi; CAH00663; CAH00663; KLLA0_D11352g.
DR GeneID; 2893280; -.
DR KEGG; kla:KLLA0_D11352g; -.
DR eggNOG; KOG1369; Eukaryota.
DR HOGENOM; CLU_014393_5_2_1; -.
DR InParanoid; P33284; -.
DR OMA; IAINCEW; -.
DR BRENDA; 2.7.1.1; 2825.
DR SABIO-RK; P33284; -.
DR UniPathway; UPA00109; UER00180.
DR UniPathway; UPA00242; -.
DR EvolutionaryTrace; P33284; -.
DR Proteomes; UP000000598; Chromosome D.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0008865; F:fructokinase activity; IEA:RHEA.
DR GO; GO:0004340; F:glucokinase activity; IEA:RHEA.
DR GO; GO:0005536; F:glucose binding; IEA:InterPro.
DR GO; GO:0001678; P:cellular glucose homeostasis; IEA:InterPro.
DR GO; GO:0006096; P:glycolytic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006013; P:mannose metabolic process; IEA:UniProt.
DR InterPro; IPR043129; ATPase_NBD.
DR InterPro; IPR001312; Hexokinase.
DR InterPro; IPR019807; Hexokinase_BS.
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; PS00378; HEXOKINASE_1; 1.
DR PROSITE; PS51748; HEXOKINASE_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Allosteric enzyme; ATP-binding; Direct protein sequencing;
KW Glycolysis; Kinase; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:12882981"
FT CHAIN 2..485
FT /note="Hexokinase"
FT /id="PRO_0000197608"
FT DOMAIN 21..468
FT /note="Hexokinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT REGION 75..208
FT /note="Hexokinase small subdomain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT REGION 151..177
FT /note="Glucose-binding"
FT /evidence="ECO:0000255"
FT REGION 209..457
FT /note="Hexokinase large subdomain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT BINDING 111
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT MOD_RES 15
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:12882981"
FT CONFLICT 206
FT /note="A -> R (in Ref. 1; CAA43855)"
FT /evidence="ECO:0000305"
FT HELIX 21..34
FT /evidence="ECO:0007829|PDB:3O8M"
FT HELIX 38..56
FT /evidence="ECO:0007829|PDB:3O8M"
FT STRAND 57..59
FT /evidence="ECO:0007829|PDB:3O8M"
FT STRAND 61..63
FT /evidence="ECO:0007829|PDB:3O80"
FT STRAND 79..103
FT /evidence="ECO:0007829|PDB:3O8M"
FT STRAND 105..113
FT /evidence="ECO:0007829|PDB:3O8M"
FT HELIX 118..120
FT /evidence="ECO:0007829|PDB:3O8M"
FT HELIX 123..141
FT /evidence="ECO:0007829|PDB:3O8M"
FT STRAND 150..156
FT /evidence="ECO:0007829|PDB:3O8M"
FT STRAND 158..161
FT /evidence="ECO:0007829|PDB:3O6W"
FT STRAND 163..166
FT /evidence="ECO:0007829|PDB:3O6W"
FT HELIX 187..197
FT /evidence="ECO:0007829|PDB:3O8M"
FT STRAND 202..208
FT /evidence="ECO:0007829|PDB:3O8M"
FT HELIX 210..221
FT /evidence="ECO:0007829|PDB:3O8M"
FT STRAND 225..242
FT /evidence="ECO:0007829|PDB:3O8M"
FT HELIX 243..245
FT /evidence="ECO:0007829|PDB:3O8M"
FT HELIX 247..249
FT /evidence="ECO:0007829|PDB:3O8M"
FT TURN 250..252
FT /evidence="ECO:0007829|PDB:3O8M"
FT STRAND 262..266
FT /evidence="ECO:0007829|PDB:3O8M"
FT HELIX 269..271
FT /evidence="ECO:0007829|PDB:3O8M"
FT TURN 272..275
FT /evidence="ECO:0007829|PDB:3O8M"
FT STRAND 277..279
FT /evidence="ECO:0007829|PDB:3O8M"
FT HELIX 283..291
FT /evidence="ECO:0007829|PDB:3O8M"
FT STRAND 292..294
FT /evidence="ECO:0007829|PDB:3O8M"
FT HELIX 299..304
FT /evidence="ECO:0007829|PDB:3O8M"
FT TURN 306..308
FT /evidence="ECO:0007829|PDB:3O8M"
FT HELIX 309..322
FT /evidence="ECO:0007829|PDB:3O8M"
FT STRAND 325..327
FT /evidence="ECO:0007829|PDB:3O8M"
FT HELIX 333..336
FT /evidence="ECO:0007829|PDB:3O8M"
FT HELIX 344..351
FT /evidence="ECO:0007829|PDB:3O8M"
FT HELIX 358..368
FT /evidence="ECO:0007829|PDB:3O8M"
FT HELIX 374..406
FT /evidence="ECO:0007829|PDB:3O8M"
FT STRAND 409..417
FT /evidence="ECO:0007829|PDB:3O8M"
FT HELIX 418..422
FT /evidence="ECO:0007829|PDB:3O8M"
FT HELIX 426..438
FT /evidence="ECO:0007829|PDB:3O8M"
FT HELIX 445..447
FT /evidence="ECO:0007829|PDB:3O8M"
FT STRAND 449..454
FT /evidence="ECO:0007829|PDB:3O8M"
FT TURN 458..460
FT /evidence="ECO:0007829|PDB:3O8M"
FT HELIX 461..476
FT /evidence="ECO:0007829|PDB:3O8M"
FT STRAND 480..482
FT /evidence="ECO:0007829|PDB:3O8M"
SQ SEQUENCE 485 AA; 53610 MW; 3E93D80C92663FB0 CRC64;
MVRLGPKKPP ARKGSMADVP ANLMEQIHGL ETLFTVSSEK MRSIVKHFIS ELDKGLSKKG
GNIPMIPGWV VEYPTGKETG DFLALDLGGT NLRVVLVKLG GNHDFDTTQN KYRLPDHLRT
GTSEQLWSFI AKCLKEFVDE WYPDGVSEPL PLGFTFSYPA SQKKINSGVL QRWTKGFDIE
GVEGHDVVPM LQEQIEKLNI PINVVALIND TTGTLVASLY TDPQTKMGII IGTGVNGAYY
DVVSGIEKLE GLLPEDIGPD SPMAINCEYG SFDNEHLVLP RTKYDVIIDE ESPRPGQQAF
EKMTSGYYLG EIMRLVLLDL YDSGFIFKDQ DISKLKEAYV MDTSYPSKIE DDPFENLEDT
DDLFKTNLNI ETTVVERKLI RKLAELVGTR AARLTVCGVS AICDKRGYKT AHIAADGSVF
NRYPGYKEKA AQALKDIYNW DVEKMEDHPI QLVAAEDGSG VGAAIIACLT QKRLAAGKSV
GIKGE
