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 24-JAN-2024, entry version 155. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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.ENSRNOP00000068888; -. DR ChEMBL; CHEMBL3632; -. DR iPTMnet; P27926; -. DR PhosphoSitePlus; P27926; -. DR jPOST; P27926; -. DR PaxDb; 10116-ENSRNOP00000031587; -. DR GeneID; 25060; -. DR KEGG; rno:25060; -. DR UCSC; RGD:2798; rat. DR AGR; RGD:2798; -. DR CTD; 3101; -. DR RGD; 2798; Hk3. DR eggNOG; KOG1369; Eukaryota. DR InParanoid; P27926; -. DR OrthoDB; 5481886at2759; -. 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: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:0001678; P:intracellular glucose homeostasis; IBA:GO_Central. DR GO; GO:1901299; P:negative regulation of hydrogen peroxide-mediated programmed cell death; IDA:CACAO. DR CDD; cd00012; NBD_sugar-kinase_HSP70_actin; 2. DR Gene3D; 3.30.420.40; -; 2. DR Gene3D; 3.40.367.20; -; 2. 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; HEXOKINASE; 1. DR PANTHER; PTHR19443:SF1; HEXOKINASE-3; 1. DR Pfam; PF00349; Hexokinase_1; 2. DR Pfam; PF03727; Hexokinase_2; 2. DR PRINTS; PR00475; HEXOKINASE. DR SUPFAM; SSF53067; Actin-like ATPase domain; 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 //