HXK1_MOUSE
ID HXK1_MOUSE Reviewed; 974 AA.
AC P17710; E9PXQ3; Q61659; Q64476; Q64479;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 3.
DT 03-AUG-2022, entry version 205.
DE RecName: Full=Hexokinase-1 {ECO:0000305};
DE EC=2.7.1.1 {ECO:0000250|UniProtKB:P19367};
DE AltName: Full=Hexokinase type I {ECO:0000303|PubMed:9450953};
DE Short=HK I {ECO:0000303|PubMed:9450953};
DE AltName: Full=Hexokinase, tumor isozyme {ECO:0000303|PubMed:2318862};
GN Name=Hk1 {ECO:0000312|MGI:MGI:96103};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM HK1).
RX PubMed=2318862; DOI=10.1016/s0021-9258(19)39352-4;
RA Arora K.K., Fanciulli M., Pedersen P.L.;
RT "Glucose phosphorylation in tumor cells. Cloning, sequencing, and
RT overexpression in active form of a full-length cDNA encoding a
RT mitochondrial bindable form of hexokinase.";
RL J. Biol. Chem. 265:6481-6488(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS HK1-SA; HK1-SB AND HK1-SC), AND
RP DEVELOPMENTAL STAGE.
RC STRAIN=CD-1; TISSUE=Testis;
RX PubMed=8396993; DOI=10.1095/biolreprod49.2.191;
RA Mori C., Welch J.E., Fulcher K.D., O'Brien D.A., Eddy E.M.;
RT "Unique hexokinase messenger ribonucleic acids lacking the porin-binding
RT domain are developmentally expressed in mouse spermatogenic cells.";
RL Biol. Reprod. 49:191-203(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP PROTEIN SEQUENCE OF 81-98; 110-118; 134-147; 203-215; 219-229; 233-243;
RP 300-310; 352-363; 372-409; 415-437; 438-452; 464-474; 489-518; 538-544;
RP 549-595; 652-663; 681-694; 784-794; 800-819; 826-833; 842-884; 906-922 AND
RP 942-974.
RC STRAIN=C57BL/6J; TISSUE=Brain;
RA Lubec G., Kang S.U.;
RL Submitted (APR-2007) to UniProtKB.
RN [5]
RP SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND PHOSPHORYLATION.
RX PubMed=9450953; DOI=10.1091/mbc.9.2.263;
RA Travis A.J., Foster J.A., Rosenbaum N.A., Visconti P.E., Gerton G.L.,
RA Kopf G.S., Moss S.B.;
RT "Targeting of a germ cell-specific type 1 hexokinase lacking a porin-
RT binding domain to the mitochondria as well as to the head and fibrous
RT sheath of murine spermatozoa.";
RL Mol. Biol. Cell 9:263-276(1998).
RN [6]
RP MUTAGENESIS OF PRO-67; LYS-68; ARG-70; LEU-73; THR-74 AND GLU-75.
RX PubMed=10567428; DOI=10.1074/jbc.274.48.34467;
RA Travis A.J., Sui D., Riedel K.D., Hofmann N.R., Moss S.B., Wilson J.E.,
RA Kopf G.S.;
RT "A novel NH(2)-terminal, nonhydrophobic motif targets a male germ cell-
RT specific hexokinase to the endoplasmic reticulum and plasma membrane.";
RL J. Biol. Chem. 274:34467-34475(1999).
RN [7]
RP INTERACTION WITH PFKM.
RX PubMed=19889946; DOI=10.1095/biolreprod.109.080580;
RA Nakamura N., Mori C., Eddy E.M.;
RT "Molecular complex of three testis-specific isozymes associated with the
RT mouse sperm fibrous sheath: hexokinase 1, phosphofructokinase M, and
RT glutathione S-transferase mu class 5.";
RL Biol. Reprod. 82:504-515(2010).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
RP INTERACTION WITH RABL2, AND TISSUE SPECIFICITY.
RX PubMed=23055941; DOI=10.1371/journal.pgen.1002969;
RA Lo J.C., Jamsai D., O'Connor A.E., Borg C., Clark B.J., Whisstock J.C.,
RA Field M.C., Adams V., Ishikawa T., Aitken R.J., Whittle B., Goodnow C.C.,
RA Ormandy C.J., O'Bryan M.K.;
RT "RAB-like 2 has an essential role in male fertility, sperm intra-flagellar
RT transport, and tail assembly.";
RL PLoS Genet. 8:E1002969-E1002969(2012).
RN [10]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=27374331; DOI=10.1016/j.cell.2016.05.076;
RA Wolf A.J., Reyes C.N., Liang W., Becker C., Shimada K., Wheeler M.L.,
RA Cho H.C., Popescu N.I., Coggeshall K.M., Arditi M., Underhill D.M.;
RT "Hexokinase is an innate immune receptor for the detection of bacterial
RT peptidoglycan.";
RL Cell 166:624-636(2016).
CC -!- FUNCTION: Catalyzes the phosphorylation of various hexoses, such as D-
CC glucose, D-glucosamine, D-fructose, D-mannose and 2-deoxy-D-glucose, to
CC hexose 6-phosphate (D-glucose 6-phosphate, D-glucosamine 6-phosphate,
CC D-fructose 6-phosphate, D-mannose 6-phosphate and 2-deoxy-D-glucose 6-
CC phosphate, respectively). Does not phosphorylate N-acetyl-D-glucosamine
CC (By similarity). Mediates the initial step of glycolysis by catalyzing
CC phosphorylation of D-glucose to D-glucose 6-phosphate (By similarity).
CC Involved in innate immunity and inflammation by acting as a pattern
CC recognition receptor for bacterial peptidoglycan. When released in the
CC cytosol, N-acetyl-D-glucosamine component of bacterial peptidoglycan
CC inhibits the hexokinase activity of HK1 and causes its dissociation
CC from mitochondrial outer membrane, thereby activating the NLRP3
CC inflammasome (PubMed:27374331). {ECO:0000250|UniProtKB:P05708,
CC ECO:0000250|UniProtKB:P19367, ECO:0000269|PubMed:27374331}.
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:0000250|UniProtKB:P19367};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22741;
CC Evidence={ECO:0000250|UniProtKB:P19367};
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:0000250|UniProtKB:P05708};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16126;
CC Evidence={ECO:0000250|UniProtKB:P05708};
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:0000250|UniProtKB:P05708};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17826;
CC Evidence={ECO:0000250|UniProtKB:P05708};
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:0000250|UniProtKB:P05708};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11029;
CC Evidence={ECO:0000250|UniProtKB:P05708};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + D-glucosamine = ADP + D-glucosamine 6-phosphate + H(+);
CC Xref=Rhea:RHEA:10948, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:58723, ChEBI:CHEBI:58725, ChEBI:CHEBI:456216; EC=2.7.1.1;
CC Evidence={ECO:0000250|UniProtKB:P19367};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10949;
CC Evidence={ECO:0000250|UniProtKB:P19367};
CC -!- ACTIVITY REGULATION: Hexokinase is an allosteric enzyme inhibited by
CC its product D-glucose 6-phosphate. Hexokinase activity is inhibited by
CC N-acetyl-D-glucosamine. {ECO:0000250|UniProtKB:P19367}.
CC -!- PATHWAY: Carbohydrate metabolism; hexose metabolism.
CC {ECO:0000250|UniProtKB:P19367}.
CC -!- PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-
CC phosphate and glycerone phosphate from D-glucose: step 1/4.
CC {ECO:0000250|UniProtKB:P05708}.
CC -!- SUBUNIT: Monomer (By similarity). Interacts with RABL2/RABL2A; binds
CC preferentially to GTP-bound RABL2 (PubMed:23055941). Interacts with
CC VDAC1. The HK1-VDAC1 complex interacts with ATF2 (By similarity).
CC Interacts (via N-terminal spermatogenic cell-specific region) with PFKM
CC isoform 2 and isoform 3 (via C-terminus) (PubMed:19889946).
CC {ECO:0000250|UniProtKB:P19367, ECO:0000269|PubMed:19889946,
CC ECO:0000269|PubMed:23055941}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane
CC {ECO:0000269|PubMed:27374331}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P19367}. Cytoplasm, cytosol
CC {ECO:0000269|PubMed:27374331}. Note=The mitochondrial-binding peptide
CC (MBP) region promotes association with the mitochondrial outer membrane
CC (By similarity). Dissociates from the mitochondrial outer membrane
CC following inhibition by N-acetyl-D-glucosamine, leading to relocation
CC to the cytosol (PubMed:27374331). {ECO:0000250|UniProtKB:P19367,
CC ECO:0000269|PubMed:27374331}.
CC -!- SUBCELLULAR LOCATION: [Isoform HK1]: Mitochondrion outer membrane
CC {ECO:0000269|PubMed:9450953}; Peripheral membrane protein
CC {ECO:0000269|PubMed:9450953}.
CC -!- SUBCELLULAR LOCATION: [Isoform HK1-SC]: Membrane
CC {ECO:0000269|PubMed:9450953}. Note=Isoform HK1-SC is an integral
CC membrane protein. {ECO:0000269|PubMed:9450953}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing, Alternative initiation; Named isoforms=4;
CC Name=HK1-SA {ECO:0000303|PubMed:8396993};
CC IsoId=P17710-1; Sequence=Displayed;
CC Name=HK1-SB {ECO:0000303|PubMed:8396993};
CC IsoId=P17710-2; Sequence=VSP_018747, VSP_007328;
CC Name=HK1;
CC IsoId=P17710-3; Sequence=VSP_007327;
CC Name=HK1-SC {ECO:0000303|PubMed:8396993};
CC IsoId=P17710-4; Sequence=VSP_018747;
CC -!- TISSUE SPECIFICITY: In rapidly growing tumor cells exhibiting high
CC glucose catabolic rates, isoform HK1 is markedly elevated. Isoform HK1-
CC SA, isoform HK1-SB and isoform HK1-SC are found only in spermatogenic
CC cells. Isoform HK1-SC is detected in round spermatids, condensing
CC spermatids and mature sperm where it is found in the head membranes,
CC mitochondria of the midpiece and the fibrous sheath of the flagellum.
CC Expressed within the principal piece and midpiece of sperm tail (at
CC protein level). {ECO:0000269|PubMed:23055941}.
CC -!- DEVELOPMENTAL STAGE: Isoform HK1-SA: First expressed during meiosis and
CC continues to be present in postmeiotic germ cells (PubMed:8396993,
CC PubMed:9450953). Isoform HK1-SB: Present only in postmeiotic germ cells
CC (PubMed:8396993). {ECO:0000269|PubMed:8396993,
CC ECO:0000269|PubMed:9450953}.
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 Each domain can bind a single D-glucose and D-glucose 6-phosphate
CC molecule. {ECO:0000250|UniProtKB:P19367}.
CC -!- PTM: [Isoform HK1-SC]: Tyrosine-phosphorylated.
CC {ECO:0000269|PubMed:9450953}.
CC -!- MISCELLANEOUS: [Isoform HK1-SB]: Produced by alternative splicing and
CC alternative initiation at Met-53 of isoform HK1-SA. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform HK1-SC]: Produced by alternative initiation at
CC Met-53 of isoform HK1-SA. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the hexokinase family. {ECO:0000255|PROSITE-
CC ProRule:PRU01084, ECO:0000305}.
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DR EMBL; J05277; AAA37804.1; -; mRNA.
DR EMBL; L16948; AAB57760.1; -; mRNA.
DR EMBL; L16949; AAB57759.1; -; mRNA.
DR EMBL; L16950; AAA53036.1; -; mRNA.
DR EMBL; AC126428; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC145297; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS48577.1; -. [P17710-3]
DR CCDS; CCDS48578.1; -. [P17710-2]
DR PIR; A35244; A35244.
DR PIR; I49744; I49744.
DR RefSeq; XP_006513305.1; XM_006513242.1. [P17710-1]
DR RefSeq; XP_006513306.1; XM_006513243.3. [P17710-4]
DR RefSeq; XP_006513307.1; XM_006513244.3. [P17710-4]
DR RefSeq; XP_006513308.1; XM_006513245.3. [P17710-4]
DR AlphaFoldDB; P17710; -.
DR SMR; P17710; -.
DR BioGRID; 200315; 21.
DR IntAct; P17710; 6.
DR STRING; 10090.ENSMUSP00000097282; -.
DR MoonProt; P17710; -.
DR iPTMnet; P17710; -.
DR PhosphoSitePlus; P17710; -.
DR SwissPalm; P17710; -.
DR EPD; P17710; -.
DR jPOST; P17710; -.
DR MaxQB; P17710; -.
DR PaxDb; P17710; -.
DR PeptideAtlas; P17710; -.
DR PRIDE; P17710; -.
DR ProteomicsDB; 273233; -. [P17710-1]
DR ProteomicsDB; 273234; -. [P17710-2]
DR ProteomicsDB; 273235; -. [P17710-3]
DR ProteomicsDB; 273236; -. [P17710-4]
DR Antibodypedia; 2057; 862 antibodies from 42 providers.
DR DNASU; 15275; -.
DR Ensembl; ENSMUST00000072357; ENSMUSP00000072195; ENSMUSG00000037012. [P17710-2]
DR Ensembl; ENSMUST00000099691; ENSMUSP00000097282; ENSMUSG00000037012. [P17710-3]
DR Ensembl; ENSMUST00000116238; ENSMUSP00000111946; ENSMUSG00000037012. [P17710-2]
DR GeneID; 15275; -.
DR UCSC; uc007fgz.2; mouse. [P17710-2]
DR CTD; 3098; -.
DR MGI; MGI:96103; Hk1.
DR VEuPathDB; HostDB:ENSMUSG00000037012; -.
DR eggNOG; KOG1369; Eukaryota.
DR GeneTree; ENSGT00950000182787; -.
DR HOGENOM; CLU_014393_1_0_1; -.
DR InParanoid; P17710; -.
DR OMA; DKYLYTM; -.
DR OrthoDB; 1153545at2759; -.
DR TreeFam; TF314238; -.
DR BRENDA; 2.7.1.1; 3474.
DR Reactome; R-MMU-70171; Glycolysis.
DR SABIO-RK; P17710; -.
DR UniPathway; UPA00109; UER00180.
DR UniPathway; UPA00242; -.
DR BioGRID-ORCS; 15275; 5 hits in 75 CRISPR screens.
DR ChiTaRS; Hk1; mouse.
DR PRO; PR:P17710; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; P17710; protein.
DR Bgee; ENSMUSG00000037012; Expressed in retinal neural layer and 253 other tissues.
DR ExpressionAtlas; P17710; baseline and differential.
DR Genevisible; P17710; MM.
DR GO; GO:0005901; C:caveola; ISO:MGI.
DR GO; GO:0005829; C:cytosol; IDA:CAFA.
DR GO; GO:0045121; C:membrane raft; IDA:MGI.
DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IDA:CAFA.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; ISO:MGI.
DR GO; GO:0008865; F:fructokinase activity; ISS:UniProtKB.
DR GO; GO:0004340; F:glucokinase activity; IDA:MGI.
DR GO; GO:0047931; F:glucosamine kinase activity; IEA:RHEA.
DR GO; GO:0005536; F:glucose binding; ISO:MGI.
DR GO; GO:0004396; F:hexokinase activity; IDA:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0019158; F:mannokinase activity; ISS:UniProtKB.
DR GO; GO:0042834; F:peptidoglycan binding; IDA:CAFA.
DR GO; GO:0004672; F:protein kinase activity; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0061621; P:canonical glycolysis; IDA:MGI.
DR GO; GO:0046835; P:carbohydrate phosphorylation; IMP:CAFA.
DR GO; GO:0001678; P:cellular glucose homeostasis; IBA:GO_Central.
DR GO; GO:0072655; P:establishment of protein localization to mitochondrion; ISO:MGI.
DR GO; GO:0006002; P:fructose 6-phosphate metabolic process; ISS:UniProtKB.
DR GO; GO:0051156; P:glucose 6-phosphate metabolic process; ISS:UniProtKB.
DR GO; GO:0006006; P:glucose metabolic process; IBA:GO_Central.
DR GO; GO:0006096; P:glycolytic process; ISO:MGI.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0072656; P:maintenance of protein location in mitochondrion; ISO:MGI.
DR GO; GO:0006013; P:mannose metabolic process; ISS:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISO:MGI.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; ISO:MGI.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; ISO:MGI.
DR GO; GO:0002720; P:positive regulation of cytokine production involved in immune response; IDA:CAFA.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; IDA:CAFA.
DR GO; GO:0046777; P:protein autophosphorylation; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; ISO:MGI.
DR GO; GO:0010359; P:regulation of anion channel activity; ISO:MGI.
DR GO; GO:0002931; P:response to ischemia; ISO:MGI.
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; 2.
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; Alternative initiation; Alternative splicing;
KW ATP-binding; Cytoplasm; Direct protein sequencing; Glycolysis; Immunity;
KW Inflammatory response; Innate immunity; Kinase; Membrane; Mitochondrion;
KW Mitochondrion outer membrane; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Repeat; Transferase.
FT CHAIN 1..974
FT /note="Hexokinase-1"
FT /id="PRO_0000013399"
FT DOMAIN 72..514
FT /note="Hexokinase 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT DOMAIN 520..962
FT /note="Hexokinase 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT REGION 1..42
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 57..66
FT /note="Mitochondrial-binding peptide (MBP)"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT REGION 129..263
FT /note="Hexokinase small subdomain 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT REGION 264..503
FT /note="Hexokinase large subdomain 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT REGION 577..711
FT /note="Hexokinase small subdomain 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT REGION 712..951
FT /note="Hexokinase large subdomain 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT BINDING 86
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 140..147
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 140..145
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 211
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 228..229
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 264..265
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 265
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 288
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 291
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 316
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 347..350
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 469..471
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 481..482
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 505
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 588..593
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 588..592
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 659..660
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 676..677
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 712..713
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 713
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 736
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 736
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 738..739
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 764
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 798
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 803..804
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 840..844
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 917..919
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 919..923
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 953
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT MOD_RES 393
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P05708"
FT VAR_SEQ 1..76
FT /note="MGWGAPLLSRMLHGPGQAGETSPVPERQSGSENPASEDRRPLEKQCSHHLYT
FT MGQNCQRGQAVDVEPKIRPPLTEE -> MIAAQLLAYYFTELKDDQVK (in
FT isoform HK1)"
FT /evidence="ECO:0000303|PubMed:2318862"
FT /id="VSP_007327"
FT VAR_SEQ 1..52
FT /note="Missing (in isoform HK1-SB and isoform HK1-SC)"
FT /evidence="ECO:0000303|PubMed:8396993"
FT /id="VSP_018747"
FT VAR_SEQ 400
FT /note="T -> TGWELSPDRRWYQAYMRCTQDTHR (in isoform HK1-SB)"
FT /evidence="ECO:0000303|PubMed:8396993"
FT /id="VSP_007328"
FT MUTAGEN 67
FT /note="P->A: Disrupts targeting to membrane; when
FT associated with N-68; Q-70; P-73; A-74 and Q-75."
FT /evidence="ECO:0000269|PubMed:10567428"
FT MUTAGEN 68
FT /note="K->N: Disrupts targeting to membrane; when
FT associated with A-67; Q-70; P-73; A-74 and Q-75."
FT /evidence="ECO:0000269|PubMed:10567428"
FT MUTAGEN 70
FT /note="R->Q: Disrupts targeting to membrane; when
FT associated with A-67; N-68; P-73; A-74 and Q-75."
FT /evidence="ECO:0000269|PubMed:10567428"
FT MUTAGEN 73
FT /note="L->P: Disrupts targeting to membrane; when
FT associated with A-67; N-68; Q-70; A-74 and Q-75."
FT /evidence="ECO:0000269|PubMed:10567428"
FT MUTAGEN 74
FT /note="T->A: Disrupts targeting to membrane; when
FT associated with A-67; N-68; Q-70; P-73 and Q-75."
FT /evidence="ECO:0000269|PubMed:10567428"
FT MUTAGEN 75
FT /note="E->Q: Disrupts targeting to membrane; when
FT associated with A-67; N-68; Q-70; P-73 and A-74."
FT /evidence="ECO:0000269|PubMed:10567428"
FT CONFLICT 870
FT /note="D -> S (in Ref. 1; AAA37804)"
FT /evidence="ECO:0000305"
FT CONFLICT 899
FT /note="E -> Q (in Ref. 2; AAB57759)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 974 AA; 108303 MW; 6122505622F7BA3D CRC64;
MGWGAPLLSR MLHGPGQAGE TSPVPERQSG SENPASEDRR PLEKQCSHHL YTMGQNCQRG
QAVDVEPKIR PPLTEEKIDK YLYAMRLSDE ILIDILTRFK KEMKNGLSRD YNPTASVKML
PTFVRSIPDG SEKGDFIALD LGGSSFRILR VQVNHEKSQN VSMESEVYDT PENIVHGSGS
QLFDHVAECL GDFMEKRKIK DKKLPVGFTF SFPCRQSKID EAVLITWTKR FKASGVEGAD
VVKLLNKAIK KRGDYDANIV AVVNDTVGTM MTCGYDDQQC EVGLIIGTGT NACYMEELRH
IDLVEGDEGR MCINTEWGAF GDDGSLEDIR TEFDRELDRG SLNPGKQLFE KMVSGMYMGE
LVRLILVKMA KESLLFEGRI TPELLTRGKF TTSDVAAIET DKEGVQNAKE ILTRLGVEPS
HDDCVSVQHV CTIVSFRSAN LVAATLGAIL NRLRDNKGTP RLRTTVGVDG SLYKMHPQYS
RRFHKTLRRL VPDSDVRFLL SESGSGKGAA MVTAVAYRLA EQHRQIEETL SHFRLSKQAL
MEVKKKLRSE MEMGLRKETN SRATVKMLPS YVRSIPDGTE HGDFLALDLG GTNFRVLLVK
IRSGKKRTVE MHNKIYSIPL EIMQGTGDEL FDHIVSCISD FLDYMGIKGP RMPLGFTFSF
PCKQTSLDCG ILITWTKGFK ATDCVGHDVA TLLRDAVKRR EEFDLDVVAV VNDTVGTMMT
CAYEEPSCEI GLIVGTGSNA CYMEEMKNVE MVEGNQGQMC INMEWGAFGD NGCLDDIRTD
FDKVVDEYSL NSGKQRFEKM ISGMYLGEIV RNILIDFTKK GFLFRGQISE PLKTRGIFET
KFLSQIESDR LALLQVRAIL QQLGLNSTCD DSILVKTVCG VVSKRAAQLC GAGMAAVVEK
IRENRGLDHL NVTVGVDGTL YKLHPHFSRI MHQTVKELSP KCTVSFLLSE DGSGKGAALI
TAVGVRLRGD PTNA
