HXKA_YEAST
ID HXKA_YEAST Reviewed; 485 AA.
AC P04806; D6VTT6;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 2.
DT 03-AUG-2022, entry version 218.
DE RecName: Full=Hexokinase-1;
DE EC=2.7.1.1 {ECO:0000305|PubMed:332086};
DE AltName: Full=Hexokinase PI;
DE AltName: Full=Hexokinase-A;
GN Name=HXK1; Synonyms=HKA; OrderedLocusNames=YFR053C;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3003701; DOI=10.1093/nar/14.2.945;
RA Stachelek C., Stachelek J., Swan J., Botstein D., Konigsberg W.;
RT "Identification, cloning and sequence determination of the genes specifying
RT hexokinase A and B from yeast.";
RL Nucleic Acids Res. 14:945-963(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3908224; DOI=10.1016/0378-1119(85)90113-1;
RA Kopetzki E., Entian K.-D., Mecke D.;
RT "Complete nucleotide sequence of the hexokinase PI gene (HXK1) of
RT Saccharomyces cerevisiae.";
RL Gene 39:95-102(1985).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=7670463; DOI=10.1038/ng0795-261;
RA Murakami Y., Naitou M., Hagiwara H., Shibata T., Ozawa M., Sasanuma S.,
RA Sasanuma M., Tsuchiya Y., Soeda E., Yokoyama K., Yamazaki M., Tashiro H.,
RA Eki T.;
RT "Analysis of the nucleotide sequence of chromosome VI from Saccharomyces
RT cerevisiae.";
RL Nat. Genet. 10:261-268(1995).
RN [4]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204511 / S288c / AB972;
RX PubMed=8686379;
RX DOI=10.1002/(sici)1097-0061(199602)12:2<149::aid-yea893>3.0.co;2-g;
RA Eki T., Naitou M., Hagiwara H., Ozawa M., Sasanuma S., Sasanuma M.,
RA Tsuchiya Y., Shibata T., Hanaoka F., Murakami Y.;
RT "Analysis of a 36.2 kb DNA sequence including the right telomere of
RT chromosome VI from Saccharomyces cerevisiae.";
RL Yeast 12:149-167(1996).
RN [6]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=332086; DOI=10.1016/0003-9861(77)90544-6;
RA Lobo Z., Maitra P.K.;
RT "Physiological role of glucose-phosphorylating enzymes in Saccharomyces
RT cerevisiae.";
RL Arch. Biochem. Biophys. 182:639-645(1977).
RN [7]
RP ATP-BINDING, AND PROTEIN SEQUENCE OF 104-112.
RX PubMed=3131329; DOI=10.1016/s0021-9258(18)68583-7;
RA Tamura J.K., Ladime J.R., Cross R.L.;
RT "The adenine nucleotide binding site on yeast hexokinase PII. Affinity
RT labeling of Lys-111 by pyridoxal 5'-diphospho-5'-adenosine.";
RL J. Biol. Chem. 263:7907-7912(1988).
RN [8]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-245 AND SER-272, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT "A multidimensional chromatography technology for in-depth phosphoproteome
RT analysis.";
RL Mol. Cell. Proteomics 7:1389-1396(2008).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19779198; DOI=10.1126/science.1172867;
RA Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT "Global analysis of Cdk1 substrate phosphorylation sites provides insights
RT into evolution.";
RL Science 325:1682-1686(2009).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (3.5 ANGSTROMS).
RX PubMed=7001031; DOI=10.1016/0022-2836(80)90102-3;
RA Bennett W.S. Jr., Steitz T.A.;
RT "Structure of a complex between yeast hexokinase A and glucose. I.
RT Structure determination and refinement at 3.5-A resolution.";
RL J. Mol. Biol. 140:183-210(1980).
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:332086). Mediates the
CC initial step of glycolysis by catalyzing phosphorylation of D-glucose
CC to D-glucose 6-phosphate (PubMed:332086). {ECO:0000269|PubMed:332086}.
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:0000305|PubMed:332086};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22741;
CC Evidence={ECO:0000305|PubMed:332086};
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:0000305|PubMed:332086};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16126;
CC Evidence={ECO:0000305|PubMed:332086};
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:0000305|PubMed:332086};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17826;
CC Evidence={ECO:0000305|PubMed:332086};
CC -!- ACTIVITY REGULATION: Subject to allosteric control. Substrate
CC inhibition by ATP.
CC -!- PATHWAY: Carbohydrate metabolism; hexose metabolism.
CC {ECO:0000305|PubMed:332086}.
CC -!- PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-
CC phosphate and glycerone phosphate from D-glucose: step 1/4.
CC {ECO:0000305|PubMed:332086}.
CC -!- SUBUNIT: Homodimer.
CC -!- MISCELLANEOUS: In yeast there are three glucose-phosphorylating
CC isoenzymes, designated hexokinase I, II and glucokinase.
CC -!- MISCELLANEOUS: Present with 40800 molecules/cell in log phase SD
CC medium. {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the hexokinase family. {ECO:0000255|PROSITE-
CC ProRule:PRU01084, ECO:0000305}.
CC -!- WEB RESOURCE: Name=Worthington enzyme manual;
CC URL="https://www.worthington-biochem.com/HK/";
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DR EMBL; M14410; AAA34698.1; -; mRNA.
DR EMBL; X03482; CAA27202.1; -; Genomic_DNA.
DR EMBL; D50617; BAA09292.1; -; Genomic_DNA.
DR EMBL; BK006940; DAA12496.1; -; Genomic_DNA.
DR PIR; S56308; KIBYHA.
DR RefSeq; NP_116711.3; NM_001180018.3.
DR PDB; 1HKG; X-ray; 3.50 A; A=152-466.
DR PDB; 3B8A; X-ray; 2.95 A; X=1-485.
DR PDBsum; 1HKG; -.
DR PDBsum; 3B8A; -.
DR AlphaFoldDB; P04806; -.
DR SMR; P04806; -.
DR BioGRID; 31211; 106.
DR DIP; DIP-5377N; -.
DR IntAct; P04806; 96.
DR MINT; P04806; -.
DR STRING; 4932.YFR053C; -.
DR BindingDB; P04806; -.
DR iPTMnet; P04806; -.
DR SWISS-2DPAGE; P04806; -.
DR MaxQB; P04806; -.
DR PaxDb; P04806; -.
DR PRIDE; P04806; -.
DR TopDownProteomics; P04806; -.
DR EnsemblFungi; YFR053C_mRNA; YFR053C; YFR053C.
DR GeneID; 850614; -.
DR KEGG; sce:YFR053C; -.
DR SGD; S000001949; HXK1.
DR VEuPathDB; FungiDB:YFR053C; -.
DR eggNOG; KOG1369; Eukaryota.
DR GeneTree; ENSGT00950000182787; -.
DR HOGENOM; CLU_014393_5_2_1; -.
DR InParanoid; P04806; -.
DR OMA; HLRYICE; -.
DR BioCyc; MetaCyc:YFR053C-MON; -.
DR BioCyc; YEAST:YFR053C-MON; -.
DR BRENDA; 2.7.1.1; 984.
DR Reactome; R-SCE-170822; Regulation of Glucokinase by Glucokinase Regulatory Protein.
DR Reactome; R-SCE-6798695; Neutrophil degranulation.
DR Reactome; R-SCE-70171; Glycolysis.
DR SABIO-RK; P04806; -.
DR UniPathway; UPA00109; UER00180.
DR UniPathway; UPA00242; -.
DR ChiTaRS; HXK1; yeast.
DR EvolutionaryTrace; P04806; -.
DR PRO; PR:P04806; -.
DR Proteomes; UP000002311; Chromosome VI.
DR RNAct; P04806; protein.
DR GO; GO:0005737; C:cytoplasm; IDA:SGD.
DR GO; GO:0005829; C:cytosol; HDA:SGD.
DR GO; GO:0005739; C:mitochondrion; IDA:SGD.
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:0005536; F:glucose binding; IEA:InterPro.
DR GO; GO:0004396; F:hexokinase activity; IDA:SGD.
DR GO; GO:0019158; F:mannokinase activity; IBA:GO_Central.
DR GO; GO:0046835; P:carbohydrate phosphorylation; IBA:GO_Central.
DR GO; GO:0001678; P:cellular glucose homeostasis; IBA:GO_Central.
DR GO; GO:1990539; P:fructose import across plasma membrane; IGI:SGD.
DR GO; GO:0006000; P:fructose metabolic process; IMP:SGD.
DR GO; GO:0051156; P:glucose 6-phosphate metabolic process; IBA:GO_Central.
DR GO; GO:0046323; P:glucose import; IGI:SGD.
DR GO; GO:0006006; P:glucose metabolic process; IMP:SGD.
DR GO; GO:0006096; P:glycolytic process; IDA:SGD.
DR GO; GO:0006013; P:mannose metabolic process; IDA:SGD.
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 CHAIN 1..485
FT /note="Hexokinase-1"
FT /id="PRO_0000197601"
FT DOMAIN 21..468
FT /note="Hexokinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT REGION 75..209
FT /note="Hexokinase small subdomain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT REGION 210..457
FT /note="Hexokinase large subdomain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT BINDING 86..91
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 111
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT BINDING 158
FT /ligand="substrate"
FT BINDING 175..176
FT /ligand="substrate"
FT BINDING 210..211
FT /ligand="substrate"
FT BINDING 237
FT /ligand="substrate"
FT BINDING 269
FT /ligand="substrate"
FT BINDING 302
FT /ligand="substrate"
FT BINDING 307..308
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 344..348
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 419..423
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT MOD_RES 245
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18407956"
FT MOD_RES 272
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18407956"
FT CONFLICT 61
FT /note="G -> V (in Ref. 1; CAA27202)"
FT /evidence="ECO:0000305"
FT CONFLICT 103
FT /note="H -> R (in Ref. 1; CAA27202)"
FT /evidence="ECO:0000305"
FT CONFLICT 194
FT /note="N -> K (in Ref. 1; CAA27202)"
FT /evidence="ECO:0000305"
FT CONFLICT 244
FT /note="V -> C (in Ref. 1; CAA27202)"
FT /evidence="ECO:0000305"
FT CONFLICT 356..357
FT /note="EN -> VF (in Ref. 2; AAA34698)"
FT /evidence="ECO:0000305"
FT CONFLICT 364
FT /note="I -> M (in Ref. 1; CAA27202)"
FT /evidence="ECO:0000305"
FT CONFLICT 388
FT /note="I -> T (in Ref. 2; AAA34698)"
FT /evidence="ECO:0000305"
FT CONFLICT 444
FT /note="D -> EN (in Ref. 1; CAA27202)"
FT /evidence="ECO:0000305"
FT CONFLICT 479..480
FT /note="SL -> VS (in Ref. 1; CAA27202)"
FT /evidence="ECO:0000305"
FT HELIX 21..34
FT /evidence="ECO:0007829|PDB:3B8A"
FT HELIX 38..54
FT /evidence="ECO:0007829|PDB:3B8A"
FT STRAND 57..59
FT /evidence="ECO:0007829|PDB:3B8A"
FT STRAND 80..87
FT /evidence="ECO:0007829|PDB:3B8A"
FT STRAND 89..99
FT /evidence="ECO:0007829|PDB:3B8A"
FT STRAND 101..113
FT /evidence="ECO:0007829|PDB:3B8A"
FT HELIX 116..120
FT /evidence="ECO:0007829|PDB:3B8A"
FT HELIX 125..141
FT /evidence="ECO:0007829|PDB:3B8A"
FT STRAND 151..156
FT /evidence="ECO:0007829|PDB:3B8A"
FT HELIX 181..183
FT /evidence="ECO:0007829|PDB:3B8A"
FT HELIX 188..196
FT /evidence="ECO:0007829|PDB:3B8A"
FT HELIX 197..199
FT /evidence="ECO:0007829|PDB:3B8A"
FT STRAND 202..209
FT /evidence="ECO:0007829|PDB:3B8A"
FT HELIX 211..220
FT /evidence="ECO:0007829|PDB:3B8A"
FT STRAND 226..243
FT /evidence="ECO:0007829|PDB:3B8A"
FT HELIX 244..246
FT /evidence="ECO:0007829|PDB:3B8A"
FT HELIX 248..250
FT /evidence="ECO:0007829|PDB:3B8A"
FT STRAND 263..267
FT /evidence="ECO:0007829|PDB:3B8A"
FT HELIX 270..272
FT /evidence="ECO:0007829|PDB:3B8A"
FT TURN 273..276
FT /evidence="ECO:0007829|PDB:3B8A"
FT STRAND 278..280
FT /evidence="ECO:0007829|PDB:3B8A"
FT HELIX 284..292
FT /evidence="ECO:0007829|PDB:3B8A"
FT STRAND 293..295
FT /evidence="ECO:0007829|PDB:3B8A"
FT HELIX 300..303
FT /evidence="ECO:0007829|PDB:3B8A"
FT HELIX 307..322
FT /evidence="ECO:0007829|PDB:3B8A"
FT TURN 323..325
FT /evidence="ECO:0007829|PDB:3B8A"
FT STRAND 326..328
FT /evidence="ECO:0007829|PDB:3B8A"
FT TURN 334..337
FT /evidence="ECO:0007829|PDB:3B8A"
FT HELIX 345..351
FT /evidence="ECO:0007829|PDB:3B8A"
FT HELIX 359..367
FT /evidence="ECO:0007829|PDB:3B8A"
FT HELIX 375..396
FT /evidence="ECO:0007829|PDB:3B8A"
FT HELIX 398..406
FT /evidence="ECO:0007829|PDB:3B8A"
FT STRAND 410..417
FT /evidence="ECO:0007829|PDB:3B8A"
FT HELIX 419..423
FT /evidence="ECO:0007829|PDB:3B8A"
FT HELIX 427..439
FT /evidence="ECO:0007829|PDB:3B8A"
FT TURN 444..446
FT /evidence="ECO:0007829|PDB:3B8A"
FT STRAND 449..454
FT /evidence="ECO:0007829|PDB:3B8A"
FT TURN 458..460
FT /evidence="ECO:0007829|PDB:3B8A"
FT HELIX 461..475
FT /evidence="ECO:0007829|PDB:3B8A"
FT STRAND 480..482
FT /evidence="ECO:0007829|PDB:3B8A"
SQ SEQUENCE 485 AA; 53738 MW; AF5C9DA8F17BC3D0 CRC64;
MVHLGPKKPQ ARKGSMADVP KELMDEIHQL EDMFTVDSET LRKVVKHFID ELNKGLTKKG
GNIPMIPGWV MEFPTGKESG NYLAIDLGGT NLRVVLVKLS GNHTFDTTQS KYKLPHDMRT
TKHQEELWSF IADSLKDFMV EQELLNTKDT LPLGFTFSYP ASQNKINEGI LQRWTKGFDI
PNVEGHDVVP LLQNEISKRE LPIEIVALIN DTVGTLIASY YTDPETKMGV IFGTGVNGAF
YDVVSDIEKL EGKLADDIPS NSPMAINCEY GSFDNEHLVL PRTKYDVAVD EQSPRPGQQA
FEKMTSGYYL GELLRLVLLE LNEKGLMLKD QDLSKLKQPY IMDTSYPARI EDDPFENLED
TDDIFQKDFG VKTTLPERKL IRRLCELIGT RAARLAVCGI AAICQKRGYK TGHIAADGSV
YNKYPGFKEA AAKGLRDIYG WTGDASKDPI TIVPAEDGSG AGAAVIAALS EKRIAEGKSL
GIIGA
