ID HXK2_SCHPO Reviewed; 455 AA.
AC P50521; P78848;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 24-JAN-2024, entry version 153.
DE RecName: Full=Hexokinase-2 {ECO:0000303|PubMed:8549830};
DE EC=2.7.1.1 {ECO:0000269|PubMed:9790975, ECO:0000305|PubMed:8549830};
GN Name=hxk2 {ECO:0000303|PubMed:8549830}; ORFNames=SPAC4F8.07c;
OS Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Taphrinomycotina;
OC Schizosaccharomycetes; Schizosaccharomycetales; Schizosaccharomycetaceae;
OC Schizosaccharomyces.
OX NCBI_TaxID=284812;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=8549830; DOI=10.1016/0014-5793(95)01451-9;
RA Petit T., Blazquez M.A., Gancedo C.;
RT "Schizosaccharomyces pombe possesses an unusual and a conventional
RT hexokinase: biochemical and molecular characterization of both
RT hexokinases.";
RL FEBS Lett. 378:185-189(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=972 / ATCC 24843;
RX PubMed=11859360; DOI=10.1038/nature724;
RA Wood V., Gwilliam R., Rajandream M.A., Lyne M.H., Lyne R., Stewart A.,
RA Sgouros J.G., Peat N., Hayles J., Baker S.G., Basham D., Bowman S.,
RA Brooks K., Brown D., Brown S., Chillingworth T., Churcher C.M., Collins M.,
RA Connor R., Cronin A., Davis P., Feltwell T., Fraser A., Gentles S.,
RA Goble A., Hamlin N., Harris D.E., Hidalgo J., Hodgson G., Holroyd S.,
RA Hornsby T., Howarth S., Huckle E.J., Hunt S., Jagels K., James K.D.,
RA Jones L., Jones M., Leather S., McDonald S., McLean J., Mooney P.,
RA Moule S., Mungall K.L., Murphy L.D., Niblett D., Odell C., Oliver K.,
RA O'Neil S., Pearson D., Quail M.A., Rabbinowitsch E., Rutherford K.M.,
RA Rutter S., Saunders D., Seeger K., Sharp S., Skelton J., Simmonds M.N.,
RA Squares R., Squares S., Stevens K., Taylor K., Taylor R.G., Tivey A.,
RA Walsh S.V., Warren T., Whitehead S., Woodward J.R., Volckaert G., Aert R.,
RA Robben J., Grymonprez B., Weltjens I., Vanstreels E., Rieger M.,
RA Schaefer M., Mueller-Auer S., Gabel C., Fuchs M., Duesterhoeft A.,
RA Fritzc C., Holzer E., Moestl D., Hilbert H., Borzym K., Langer I., Beck A.,
RA Lehrach H., Reinhardt R., Pohl T.M., Eger P., Zimmermann W., Wedler H.,
RA Wambutt R., Purnelle B., Goffeau A., Cadieu E., Dreano S., Gloux S.,
RA Lelaure V., Mottier S., Galibert F., Aves S.J., Xiang Z., Hunt C.,
RA Moore K., Hurst S.M., Lucas M., Rochet M., Gaillardin C., Tallada V.A.,
RA Garzon A., Thode G., Daga R.R., Cruzado L., Jimenez J., Sanchez M.,
RA del Rey F., Benito J., Dominguez A., Revuelta J.L., Moreno S.,
RA Armstrong J., Forsburg S.L., Cerutti L., Lowe T., McCombie W.R.,
RA Paulsen I., Potashkin J., Shpakovski G.V., Ussery D., Barrell B.G.,
RA Nurse P.;
RT "The genome sequence of Schizosaccharomyces pombe.";
RL Nature 415:871-880(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 20-455.
RC STRAIN=PR745;
RX PubMed=9501991; DOI=10.1093/dnares/4.6.363;
RA Yoshioka S., Kato K., Nakai K., Okayama H., Nojima H.;
RT "Identification of open reading frames in Schizosaccharomyces pombe
RT cDNAs.";
RL DNA Res. 4:363-369(1997).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP MUTAGENESIS OF ASN-196.
RX PubMed=9790975; DOI=10.1006/bbrc.1998.9538;
RA Petit T., Herrero P., Gancedo C.;
RT "A mutation Ser213/Asn in the hexokinase 1 from Schizosaccharomyces pombe
RT increases its affinity for glucose.";
RL Biochem. Biophys. Res. Commun. 251:714-719(1998).
CC -!- FUNCTION: Catalyzes the phosphorylation of hexose (six-carbon sugars)
CC to hexose 6-phosphate (PubMed:8549830, PubMed:9790975). Phosphorylates
CC D-glucose, D-fructose and D-mannose (PubMed:8549830, PubMed:9790975).
CC Compared to hxk1, has a much higher affinity for D-glucose
CC (PubMed:8549830, PubMed:9790975). Constitutes the initial enzyme of
CC glycolysis by catalyzing the phosphorylation of glucose to D-glucose 6-
CC phosphate (Probable). {ECO:0000269|PubMed:8549830,
CC ECO:0000269|PubMed:9790975, ECO:0000305}.
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:9790975, ECO:0000305|PubMed:8549830};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22741;
CC Evidence={ECO:0000269|PubMed:9790975, ECO:0000305|PubMed:8549830};
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:9790975, ECO:0000305|PubMed:8549830};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11029;
CC Evidence={ECO:0000269|PubMed:9790975, ECO:0000305|PubMed:8549830};
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:9790975, ECO:0000305|PubMed:8549830};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16126;
CC Evidence={ECO:0000269|PubMed:9790975, ECO:0000305|PubMed:8549830};
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:9790975, ECO:0000305|PubMed:8549830};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17826;
CC Evidence={ECO:0000269|PubMed:9790975, ECO:0000305|PubMed:8549830};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.16 mM for D-glucose {ECO:0000269|PubMed:9790975};
CC -!- PATHWAY: Carbohydrate metabolism; hexose metabolism.
CC {ECO:0000305|PubMed:8549830}.
CC -!- PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-
CC phosphate and glycerone phosphate from D-glucose: step 1/4.
CC {ECO:0000305|PubMed:8549830}.
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:P19367}.
CC -!- SIMILARITY: Belongs to the hexokinase family. {ECO:0000255|PROSITE-
CC ProRule:PRU01084, ECO:0000305}.
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DR EMBL; X92895; CAA63488.1; -; mRNA.
DR EMBL; CU329670; CAB11054.1; -; Genomic_DNA.
DR EMBL; D89198; BAA13859.1; -; mRNA.
DR PIR; S68693; S68693.
DR PIR; T42997; T42997.
DR RefSeq; NP_593865.1; NM_001019294.2.
DR AlphaFoldDB; P50521; -.
DR SMR; P50521; -.
DR BioGRID; 280022; 10.
DR STRING; 284812.P50521; -.
DR iPTMnet; P50521; -.
DR MaxQB; P50521; -.
DR PaxDb; 4896-SPAC4F8-07c-1; -.
DR EnsemblFungi; SPAC4F8.07c.1; SPAC4F8.07c.1:pep; SPAC4F8.07c.
DR GeneID; 2543607; -.
DR KEGG; spo:SPAC4F8.07c; -.
DR PomBase; SPAC4F8.07c; hxk2.
DR VEuPathDB; FungiDB:SPAC4F8.07c; -.
DR eggNOG; KOG1369; Eukaryota.
DR HOGENOM; CLU_014393_5_0_1; -.
DR InParanoid; P50521; -.
DR OMA; YPNFEGY; -.
DR PhylomeDB; P50521; -.
DR BRENDA; 2.7.1.1; 5613.
DR Reactome; R-SPO-170822; Regulation of Glucokinase by Glucokinase Regulatory Protein.
DR Reactome; R-SPO-6798695; Neutrophil degranulation.
DR Reactome; R-SPO-70171; Glycolysis.
DR SABIO-RK; P50521; -.
DR UniPathway; UPA00109; UER00180.
DR UniPathway; UPA00242; -.
DR PRO; PR:P50521; -.
DR Proteomes; UP000002485; Chromosome I.
DR GO; GO:0005829; C:cytosol; HDA:PomBase.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; HDA:PomBase.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0008865; F:fructokinase activity; IDA:PomBase.
DR GO; GO:0004340; F:glucokinase activity; IDA:PomBase.
DR GO; GO:0005536; F:glucose binding; IEA:InterPro.
DR GO; GO:0019158; F:mannokinase activity; IDA:PomBase.
DR GO; GO:0061621; P:canonical glycolysis; NAS:PomBase.
DR GO; GO:0046835; P:carbohydrate phosphorylation; 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:0019660; P:glycolytic fermentation; IMP:PomBase.
DR GO; GO:0006096; P:glycolytic process; IBA:GO_Central.
DR GO; GO:0001678; P:intracellular glucose homeostasis; IBA:GO_Central.
DR CDD; cd00012; NBD_sugar-kinase_HSP70_actin; 1.
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; IPR019807; Hexokinase_BS.
DR InterPro; IPR022673; Hexokinase_C.
DR InterPro; IPR022672; Hexokinase_N.
DR PANTHER; PTHR19443:SF30; GLUCOKINASE-1-RELATED; 1.
DR PANTHER; PTHR19443; HEXOKINASE; 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; PS00378; HEXOKINASE_1; 1.
DR PROSITE; PS51748; HEXOKINASE_2; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Glycolysis; Kinase; Nucleotide-binding; Reference proteome;
KW Transferase.
FT CHAIN 1..455
FT /note="Hexokinase-2"
FT /id="PRO_0000197610"
FT DOMAIN 3..445
FT /note="Hexokinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT REGION 57..195
FT /note="Hexokinase small subdomain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT REGION 196..434
FT /note="Hexokinase large subdomain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT BINDING 68..73
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 144..145
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P35557"
FT BINDING 161..162
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P35557"
FT BINDING 196..197
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P35557"
FT BINDING 222
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P35557"
FT BINDING 225
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P35557"
FT BINDING 252
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P35557"
FT BINDING 283
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P35557"
FT BINDING 288..289
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P35557"
FT BINDING 325..329
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P35557"
FT BINDING 400..404
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P35557"
FT MUTAGEN 196
FT /note="N->S: Decreased affinity for D-glucose."
FT /evidence="ECO:0000269|PubMed:9790975"
FT CONFLICT 295
FT /note="F -> S (in Ref. 3; BAA13859)"
FT /evidence="ECO:0000305"
FT CONFLICT 298
FT /note="A -> V (in Ref. 3; BAA13859)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 455 AA; 50920 MW; 9751F9969F63AC96 CRC64;
MEANFQQAVK KLVNDFEYPT ESLREAVKEF DELRQKGLQK NGEVLAMAPA FISTLPTGAE
TGDFLALDFG GTNLRVCWIQ LLGDGKYEMK HSKSVLPREC VRNESVKPII DFMSDHVELF
IKEHFPSKFG CPEEEYLPMG FTFSYPANQV SITESYLLRW TKGLNIPEAI NKDFAQFLTE
GFKARNLPIR IEAVINDTVG TLVTRAYTSK ESDTFMGIIF GTGTNGAYVE QMNQIPKLAG
KCTGDHMLIN MEWGATDFSC LHSTRYDLLL DHDTPNAGRQ IFEKRVGGMY LGELFRRALF
HLIKVYNFNE GIFPPSITDA WSLETSVLSR MMVERSAENV RNVLSTFKFR FRSDEEALYL
WDAAHAIGRR AARMSAVPIA SLYLSTGRAG KKSDVGVDGS LVEHYPHFVD MLREALRELI
GDNEKLISIG IAKDGSGIGA ALCALQAVKE KKGLA
//
