HXK3_RAT
ID HXK3_RAT Reviewed; 924 AA.
AC P27926; Q497A1;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1992, sequence version 1.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Hexokinase-3 {ECO:0000305};
DE EC=2.7.1.1 {ECO:0000269|PubMed:5871820};
DE AltName: Full=Hexokinase type III {ECO:0000303|PubMed:1897938};
DE Short=HK III {ECO:0000303|PubMed:1897938};
DE AltName: Full=Hexokinase-C {ECO:0000303|PubMed:5871820};
GN Name=Hk3 {ECO:0000312|RGD:2798};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=1897938; DOI=10.1016/0003-9861(91)90373-q;
RA Schwab D.A., Wilson J.E.;
RT "Complete amino acid sequence of the type III isozyme of rat hexokinase,
RT deduced from the cloned cDNA.";
RL Arch. Biochem. Biophys. 285:365-370(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RA White J.A.;
RL Submitted (OCT-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=5871820; DOI=10.1016/0006-291x(64)90038-5;
RA Gonzalez C., Ureta T., Sanchez R., Niemeyer H.;
RT "Multiple molecular forms of ATP:hexose 6-phosphotransferase from rat
RT liver.";
RL Biochem. Biophys. Res. Commun. 16:347-352(1964).
RN [5]
RP REVIEW.
RX PubMed=7044667; DOI=10.1016/0305-0491(82)90461-8;
RA Ureta T.;
RT "The comparative isozymology of vertebrate hexokinases.";
RL Comp. Biochem. Physiol. 71:549-555(1982).
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:5871820). Mediates the
CC initial step of glycolysis by catalyzing phosphorylation of D-glucose
CC to D-glucose 6-phosphate (PubMed:5871820).
CC {ECO:0000269|PubMed:5871820}.
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:5871820};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22741;
CC Evidence={ECO:0000269|PubMed:5871820};
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:5871820};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16126;
CC Evidence={ECO:0000269|PubMed:5871820};
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:5871820};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17826;
CC Evidence={ECO:0000269|PubMed:5871820};
CC -!- ACTIVITY REGULATION: Hexokinase is an allosteric enzyme inhibited by
CC its product D-glucose 6-phosphate. {ECO:0000250|UniProtKB:P52790}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=6 uM for D-glucose {ECO:0000269|PubMed:5871820};
CC KM=1.2 mM for D-fructose {ECO:0000269|PubMed:5871820};
CC -!- PATHWAY: Carbohydrate metabolism; hexose metabolism.
CC {ECO:0000305|PubMed:5871820}.
CC -!- PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-
CC phosphate and glycerone phosphate from D-glucose: step 1/4.
CC {ECO:0000305|PubMed:5871820}.
CC -!- DOMAIN: The N- and C-terminal halves of this hexokinase contain a
CC hexokinase domain. The catalytic activity is associated with the C-
CC terminus while regulatory function is associated with the N-terminus.
CC {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; U73859; AAB18253.1; -; mRNA.
DR EMBL; BC100648; AAI00649.1; -; mRNA.
DR PIR; S13913; S13913.
DR RefSeq; NP_071515.1; NM_022179.2.
DR RefSeq; XP_006253664.1; XM_006253602.3.
DR RefSeq; XP_006253665.1; XM_006253603.3.
DR RefSeq; XP_008769706.1; XM_008771484.1.
DR AlphaFoldDB; P27926; -.
DR SMR; P27926; -.
DR BioGRID; 247137; 10.
DR STRING; 10116.ENSRNOP00000031587; -.
DR ChEMBL; CHEMBL3632; -.
DR iPTMnet; P27926; -.
DR PhosphoSitePlus; P27926; -.
DR jPOST; P27926; -.
DR PaxDb; P27926; -.
DR PRIDE; P27926; -.
DR GeneID; 25060; -.
DR KEGG; rno:25060; -.
DR UCSC; RGD:2798; rat.
DR CTD; 3101; -.
DR RGD; 2798; Hk3.
DR eggNOG; KOG1369; Eukaryota.
DR InParanoid; P27926; -.
DR OrthoDB; 1153545at2759; -.
DR PhylomeDB; P27926; -.
DR TreeFam; TF314238; -.
DR Reactome; R-RNO-6798695; Neutrophil degranulation.
DR Reactome; R-RNO-70171; Glycolysis.
DR SABIO-RK; P27926; -.
DR UniPathway; UPA00109; UER00180.
DR UniPathway; UPA00242; -.
DR PRO; PR:P27926; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019899; F:enzyme binding; IPI:RGD.
DR GO; GO:0008865; F:fructokinase activity; IDA:UniProtKB.
DR GO; GO:0004340; F:glucokinase activity; IDA:UniProtKB.
DR GO; GO:0005536; F:glucose binding; IEA:InterPro.
DR GO; GO:0004396; F:hexokinase activity; IDA:RGD.
DR GO; GO:0042562; F:hormone binding; IPI:RGD.
DR GO; GO:0046835; P:carbohydrate phosphorylation; IBA:GO_Central.
DR GO; GO:0001678; P:cellular glucose homeostasis; IBA:GO_Central.
DR GO; GO:0006002; P:fructose 6-phosphate metabolic process; IDA:UniProtKB.
DR GO; GO:0051156; P:glucose 6-phosphate metabolic process; IDA:UniProtKB.
DR GO; GO:0006006; P:glucose metabolic process; IBA:GO_Central.
DR GO; GO:0006096; P:glycolytic process; IBA:GO_Central.
DR GO; GO:1901299; P:negative regulation of hydrogen peroxide-mediated programmed cell death; IDA:CACAO.
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; 4.
DR Pfam; PF00349; Hexokinase_1; 2.
DR Pfam; PF03727; Hexokinase_2; 2.
DR SUPFAM; SSF53067; SSF53067; 4.
DR PROSITE; PS00378; HEXOKINASE_1; 2.
DR PROSITE; PS51748; HEXOKINASE_2; 2.
PE 1: Evidence at protein level;
KW Allosteric enzyme; ATP-binding; Glycolysis; Kinase; Nucleotide-binding;
KW Reference proteome; Repeat; Transferase.
FT CHAIN 1..924
FT /note="Hexokinase-3"
FT /id="PRO_0000197592"
FT DOMAIN 27..471
FT /note="Hexokinase 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT DOMAIN 477..913
FT /note="Hexokinase 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT REGION 1..27
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 84..220
FT /note="Hexokinase small subdomain 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT REGION 221..460
FT /note="Hexokinase large subdomain 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT REGION 531..662
FT /note="Hexokinase small subdomain 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT REGION 663..902
FT /note="Hexokinase large subdomain 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT BINDING 95..104
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 95..102
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 168
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 185..186
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 221..222
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 222
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 245
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 248
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 273
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 304..307
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 426..428
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 438..439
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 542..547
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 542..546
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 610..611
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 627..628
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P52790"
FT BINDING 663..664
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P52790"
FT BINDING 664
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 687
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 687
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 689..690
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P52790"
FT BINDING 715
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P52790"
FT BINDING 749
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P52790"
FT BINDING 754..755
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 791..795
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 868..870
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 870..874
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 904
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT CONFLICT 913
FT /note="R -> A (in Ref. 3; AAI00649)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 924 AA; 100254 MW; 0162C1591AF040AC CRC64;
MAAIEPSGLH PGERDSSCPQ EGIPRPSGSL ELAQEYLQQF KVTMTQLQQI QASLLCSMEQ
ALKGQDSPAP SVRMLPTYVR STPHGTEQGD FLVLELGATG ASLRVLWVTL TGTKEHSVET
RSQEFVIPQE VILGAGQQLF DFAARCLSEF LDAYPVENQG LKLGFNFSFP CHQTGLDKST
LISWTKGFRC SGVEGQDVVQ LLRDAIQRQG TYNIDVVAMV NDTVGTMMGC ELGTRPCEVG
LIVDTGTNAC YMEEARHVAA LDEDRGRTCV SIEWGSFYDE EALGPVLTTF DDALDHESLV
PGAQRFEKMI GGLYLGELVR LVLVHLSQHG VLFGGCASPA LLSQNSILLE HVAKMEDPAT
GIAHVHTVLQ GLGLSPQASD AELVQRVCMA VCTRAAQLCA SALAAVLSRL QHSREQQTLH
VAVATGGRVF EWHPRFLCIL KETVMLLAPE CDVSFIPSVD GGGRGVAMVT AVAARLATHR
RILEETLAPF QLSLEQLTAV QAQMREAMIR GLQGESSSLR MLPTYVRATP DGSERGDFLA
LDLGGTNFRV LLVRVAEGSV QITNQVYSIP EYVAQGSGQK LFDHIVDCIV DFQKRQGLSG
QSLPLGFTFS FPCKQLGLDQ GILLNWTKGF NASGCEGQDV VYLLREAIRR RQAVELNVVA
IVNDTVGTMM SCGYDDPCCE MGLIVGTGTN ACYMEELRNV ASVPGDSGHM CINMEWGAFG
DDGSLSMLGT CFDASVDQAS INPGKQRFEK MISGMYLGEI VRHILLHLTS LGVLFRGQKT
QCLQTRDIFK TKFLSEIESD SLALRQVRAI LEDLGLTLTS DDALMVLEVC QAVSRRAAQL
CGAGVAAVVE KIRENRGLQE LTVSVGVDGT LYKLHPHFSR LVSVTVRKLA PQCTVTFLQS
EDGSGKGAAL VTRVACRLTQ MACV
