ID HXK_BRUMA Reviewed; 572 AA. AC A0A0K0JFP3; Q56VN6; DT 07-SEP-2016, integrated into UniProtKB/Swiss-Prot. DT 14-OCT-2015, sequence version 1. DT 03-MAY-2023, entry version 31. DE RecName: Full=Hexokinase {ECO:0000303|PubMed:18499511}; DE Short=BmHK {ECO:0000303|PubMed:18499511}; DE EC=2.7.1.1 {ECO:0000269|PubMed:18499511}; GN ORFNames=Bm4678 {ECO:0000312|EMBL:CRZ23240.1}; OS Brugia malayi (Filarial nematode worm). OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida; OC Spirurina; Spiruromorpha; Filarioidea; Onchocercidae; Brugia. OX NCBI_TaxID=6279; RN [1] {ECO:0000312|EMBL:AAR13363.1} RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, ACTIVITY RP REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY. RX PubMed=18499511; DOI=10.1016/j.parint.2008.03.004; RA Singh A.R., Joshi S., Arya R., Kayastha A.M., Srivastava K.K., RA Tripathi L.M., Saxena J.K.; RT "Molecular cloning and characterization of Brugia malayi hexokinase."; RL Parasitol. Int. 57:354-361(2008). RN [2] {ECO:0000312|EMBL:CRZ23240.1} RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=FR3 {ECO:0000312|EMBL:CRZ23240.1}; RX PubMed=17885136; DOI=10.1126/science.1145406; RA Ghedin E., Wang S., Spiro D., Caler E., Zhao Q., Crabtree J., Allen J.E., RA Delcher A.L., Guiliano D.B., Miranda-Saavedra D., Angiuoli S.V., Creasy T., RA Amedeo P., Haas B., El-Sayed N.M., Wortman J.R., Feldblyum T., Tallon L., RA Schatz M., Shumway M., Koo H., Salzberg S.L., Schobel S., Pertea M., RA Pop M., White O., Barton G.J., Carlow C.K.S., Crawford M.J., Daub J., RA Dimmic M.W., Estes C.F., Foster J.M., Ganatra M., Gregory W.F., RA Johnson N.M., Jin J., Komuniecki R., Korf I., Kumar S., Laney S., Li B.-W., RA Li W., Lindblom T.H., Lustigman S., Ma D., Maina C.V., Martin D.M., RA McCarter J.P., McReynolds L., Mitreva M., Nutman T.B., Parkinson J., RA Peregrin-Alvarez J.M., Poole C., Ren Q., Saunders L., Sluder A.E., RA Smith K., Stanke M., Unnasch T.R., Ware J., Wei A.D., Weil G., RA Williams D.J., Zhang Y., Williams S.A., Fraser-Liggett C., Slatko B., RA Blaxter M.L., Scott A.L.; RT "Draft genome of the filarial nematode parasite Brugia malayi."; RL Science 317:1756-1760(2007). CC -!- FUNCTION: Active against glucose, fructose, mannose, maltose and CC galactose. {ECO:0000269|PubMed:18499511}. 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:0000255|PROSITE-ProRule:PRU01084, CC ECO:0000269|PubMed:18499511}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22741; CC Evidence={ECO:0000269|PubMed:18499511}; 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:18499511}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11029; CC Evidence={ECO:0000269|PubMed:18499511}; 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:18499511}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16126; CC Evidence={ECO:0000269|PubMed:18499511}; 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:18499511}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17826; CC Evidence={ECO:0000269|PubMed:18499511}; CC -!- ACTIVITY REGULATION: Activated by glucose-6-phosphate. Inhibited by N- CC acetylglucosamine, glucosamine, mannoheptulose and ADP. CC {ECO:0000269|PubMed:18499511}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=0.035 mM for glucose {ECO:0000269|PubMed:18499511}; CC KM=75 mM for fructose {ECO:0000269|PubMed:18499511}; CC KM=1.09 mM for ATP {ECO:0000269|PubMed:18499511}; CC pH dependence: CC Optimum pH is 8.4. {ECO:0000269|PubMed:18499511}; CC -!- PATHWAY: Carbohydrate metabolism; hexose metabolism. CC {ECO:0000269|PubMed:18499511}. CC -!- PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3- CC phosphate and glycerone phosphate from D-glucose: step 1/4. CC {ECO:0000269|PubMed:18499511}. CC -!- SIMILARITY: Belongs to the hexokinase family. {ECO:0000255, CC ECO:0000255|PROSITE-ProRule:PRU01084, ECO:0000255|RuleBase:RU362007}. 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; AY341346; AAR13363.1; -; mRNA. DR EMBL; LN856840; CRZ23240.1; -; Genomic_DNA. DR AlphaFoldDB; A0A0K0JFP3; -. DR SMR; A0A0K0JFP3; -. DR STRING; 6279.A0A0K0JFP3; -. DR EnsemblMetazoa; Bm4678.1; Bm4678.1; WBGene00224939. DR WormBase; Bm4678; BM38607; WBGene00224939; Bma-hxk-2. DR OrthoDB; 5481886at2759; -. DR BRENDA; 2.7.1.1; 997. DR UniPathway; UPA00109; UER00180. DR UniPathway; UPA00242; -. DR Proteomes; UP000006672; Unassembled WGS sequence. 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:0019158; F:mannokinase activity; IEA:RHEA. DR GO; GO:0006096; P:glycolytic process; IEA:UniProtKB-UniPathway. DR GO; GO:0019318; P:hexose metabolic process; IDA:UniProtKB. DR GO; GO:0001678; P:intracellular glucose homeostasis; IEA:InterPro. 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; IPR022673; Hexokinase_C. DR InterPro; IPR022672; Hexokinase_N. DR PANTHER; PTHR19443; HEXOKINASE; 1. DR PANTHER; PTHR19443:SF77; PHOSPHOTRANSFERASE; 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; PS51748; HEXOKINASE_2; 1. PE 1: Evidence at protein level; KW ATP-binding; Glycolysis; Kinase; Nucleotide-binding; Reference proteome; KW Transferase. FT CHAIN 1..572 FT /note="Hexokinase" FT /evidence="ECO:0000305" FT /id="PRO_0000437173" FT DOMAIN 49..492 FT /note="Hexokinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084" FT REGION 105..237 FT /note="Hexokinase small subdomain" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084" FT REGION 238..481 FT /note="Hexokinase large subdomain" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084" FT BINDING 116..121 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P19367" FT BINDING 116..120 FT /ligand="D-glucose 6-phosphate" FT /ligand_id="ChEBI:CHEBI:61548" FT /evidence="ECO:0000250|UniProtKB:P19367" FT BINDING 185..186 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P19367" FT BINDING 185 FT /ligand="D-glucose 6-phosphate" FT /ligand_id="ChEBI:CHEBI:61548" FT /evidence="ECO:0000250|UniProtKB:P19367" FT BINDING 202..203 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P19367" FT BINDING 238..239 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P19367" FT BINDING 239 FT /ligand="D-glucose 6-phosphate" FT /ligand_id="ChEBI:CHEBI:61548" FT /evidence="ECO:0000250|UniProtKB:P19367" FT BINDING 263 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P19367" FT BINDING 263 FT /ligand="D-glucose 6-phosphate" FT /ligand_id="ChEBI:CHEBI:61548" FT /evidence="ECO:0000250|UniProtKB:P19367" FT BINDING 266 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P19367" FT BINDING 297 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P19367" FT BINDING 331 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P19367" FT BINDING 336..337 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P19367" FT BINDING 373..377 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P19367" FT BINDING 446..448 FT /ligand="D-glucose 6-phosphate" FT /ligand_id="ChEBI:CHEBI:61548" FT /evidence="ECO:0000250|UniProtKB:P19367" FT BINDING 448..452 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P19367" FT BINDING 483 FT /ligand="D-glucose 6-phosphate" FT /ligand_id="ChEBI:CHEBI:61548" FT /evidence="ECO:0000250|UniProtKB:P19367" FT CONFLICT 68 FT /note="T -> S (in Ref. 1; AAR13363)" FT /evidence="ECO:0000305" FT CONFLICT 172 FT /note="G -> S (in Ref. 1; AAR13363)" FT /evidence="ECO:0000305" FT CONFLICT 504..509 FT /note="Missing (in Ref. 1; AAR13363)" FT /evidence="ECO:0000305" SQ SEQUENCE 572 AA; 64043 MW; C2675B140514684B CRC64; MLGLLTITSV FRNWRNSLQR KEDYDECHMR GINNENEISG KSEKNFKLDE PPISLETVMA EFKLSNETLR RMMAHMSRNM DKGLEGGPEN STISMLPSFV PELPNGTEEG RFIAMDLGGT NLRVMLMDIK PGEELKTEQF NTRIPNWAMR GTGEQLFDYI TKCLAEFLIE KGIENDGLPV GFTFSYPCDQ KSLRSATLLR WTKGFETTGV VGEDVVELLE QSIARRGDIK VEVVALINDT VGTMVAAAHE SGGECHIGVI IATGTNASYM EDTSKIKYGL SKAIAAYNYP EMIIDTEWGG FGDRSEADYI LTQYDKIVDS RSEHPGVNTF DKLVGGKCMG EVVRVVLEKL TRARVLFNGK GSDALFQQDS FPTKYISEIL RDESGSYVHT RDILGELGID HYSFSDMLLL REVCVVVSRR SANLGAAAIA CVLNRVRKQN MVVGIDGSTY KYHPFFDFWV HDKLKELVDP GLKFKLLQTA DGSGKGAALI TAIVARLKKR NLKQQQQQQQ QQQQHVTMVE QNVVEQIAET KGSREQFMNG NQKINLVTND IPIYDSFNGD IENGVIHLST DH //