HXK1_BOVIN
ID HXK1_BOVIN Reviewed; 918 AA.
AC P27595;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1992, sequence version 1.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=Hexokinase-1 {ECO:0000305};
DE EC=2.7.1.1 {ECO:0000250|UniProtKB:P19367};
DE AltName: Full=Brain form hexokinase {ECO:0000250|UniProtKB:P19367};
DE AltName: Full=Hexokinase type I {ECO:0000303|PubMed:2719857};
DE Short=HK I {ECO:0000303|PubMed:2719857};
GN Name=HK1 {ECO:0000250|UniProtKB:P19367};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2719857; DOI=10.1016/0885-4505(89)90017-0;
RA Griffin L.D., Macgregor G.R., Muzny D.M., Harter J., Cook R.G.,
RA McCabe E.R.;
RT "Synthesis and characterization of a bovine hexokinase 1 cDNA probe by
RT mixed oligonucleotide primed amplification of cDNA using high complexity
RT primer mixtures.";
RL Biochem. Med. Metab. Biol. 41:125-131(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1783373; DOI=10.1016/0888-7543(91)90027-c;
RA Griffin L.D., Gelb B.D., Wheeler D.A., Davison D., Adams V., McCabe E.R.;
RT "Mammalian hexokinase 1: evolutionary conservation and structure to
RT function analysis.";
RL Genomics 11:1014-1024(1991).
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 (By similarity). {ECO:0000250|UniProtKB:P05708,
CC ECO:0000250|UniProtKB:P19367}.
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 (By similarity). 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 (via C-terminus) (By similarity). {ECO:0000250|UniProtKB:P17710,
CC ECO:0000250|UniProtKB:P19367}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane
CC {ECO:0000250|UniProtKB:P19367}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P19367}. Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:P19367}. Note=The mitochondrial-binding peptide
CC (MBP) region promotes association with the mitochondrial outer
CC membrane. Dissociates from the mitochondrial outer membrane following
CC inhibition by N-acetyl-D-glucosamine, leading to relocation to the
CC cytosol. {ECO:0000250|UniProtKB:P19367}.
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 -!- SIMILARITY: Belongs to the hexokinase family. {ECO:0000255|PROSITE-
CC ProRule:PRU01084, ECO:0000305}.
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DR EMBL; M65140; AAA51661.1; -; mRNA.
DR PIR; A55277; A55277.
DR AlphaFoldDB; P27595; -.
DR SMR; P27595; -.
DR STRING; 9913.ENSBTAP00000016432; -.
DR PRIDE; P27595; -.
DR eggNOG; KOG1369; Eukaryota.
DR InParanoid; P27595; -.
DR SABIO-RK; P27595; -.
DR UniPathway; UPA00109; UER00180.
DR UniPathway; UPA00242; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0008865; F:fructokinase activity; ISS:UniProtKB.
DR GO; GO:0004340; F:glucokinase activity; ISS:UniProtKB.
DR GO; GO:0047931; F:glucosamine kinase activity; IEA:RHEA.
DR GO; GO:0005536; F:glucose binding; IEA:InterPro.
DR GO; GO:0019158; F:mannokinase activity; ISS:UniProtKB.
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; 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; IBA:GO_Central.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0006013; P:mannose metabolic process; ISS:UniProtKB.
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 2: Evidence at transcript level;
KW Acetylation; Allosteric enzyme; ATP-binding; Cytoplasm; Glycolysis;
KW Immunity; Inflammatory response; Innate immunity; Kinase; Membrane;
KW Mitochondrion; Mitochondrion outer membrane; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Repeat; Transferase.
FT CHAIN 1..918
FT /note="Hexokinase-1"
FT /id="PRO_0000197584"
FT DOMAIN 16..458
FT /note="Hexokinase 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT DOMAIN 464..906
FT /note="Hexokinase 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT REGION 1..10
FT /note="Mitochondrial-binding peptide (MBP)"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT REGION 73..207
FT /note="Hexokinase small subdomain 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT REGION 208..447
FT /note="Hexokinase large subdomain 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT REGION 521..655
FT /note="Hexokinase small subdomain 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT REGION 656..895
FT /note="Hexokinase large subdomain 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT BINDING 30
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 84..91
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 84..89
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 155
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 172..173
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 208..209
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 209
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 232
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 235
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 260
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 291..294
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 413..415
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 425..426
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 532..537
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 532..536
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 603..604
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 620..621
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 656..657
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 657
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 680
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 680
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 682..683
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 708
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 742
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 747..748
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 784..788
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 861..863
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 863..867
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 897
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 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT MOD_RES 337
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P05708"
SQ SEQUENCE 918 AA; 103064 MW; 1DCFB7F1D06FE2B6 CRC64;
MIAAQLLAYY FTELKDDQVK KIDKYLYAMR LSDETLLDIM NRFKKEMKNG LSRDFNPTAT
VKMLPTFVRS IPDGSEKGDF IALDLGGSSF RILRVQVNHE QNRPVHMESE VYDTPENIMH
GSGSQLFDHV LECLGDFMEK KKIKDKKLPV GFTFSFPCRQ SKIDQAILIT WTKRFKARGA
EGNYVVKLLD KAIKKRGDYD ANIVAVVNDT VGTMIDCGYD DQHCEVGLII GTGTNACYME
ELRQIDFGWG DDGRMCINTE WGDLGDDGSL EDIRKEFDRE FRRGSLNPGK QRFEKMVSGR
YMEDVVRLVL VKMAKEGLLF EGRITPELLT RGKFNTSDVS AIEKDKEGLH NAKEILTRLG
VERSDDDCVS VQHVCTIVSF RSANLVAATL GAILNRLRDN KSTPRLRTTV RVDGSLYKTH
PQYSRRFHKT LRRLVPDSDV RFLLSESGTG KGAAMVTAVA YRLAEQHRQI EETLAHFRLS
KQTLMEVKKR LRTEMEMGLR KETNSNATVN MLPSFLRSIP DGTEDGDFLA LDLGGTNFRV
LLVKIRSGKK STVEMHNKIY RIPIEIMQGT GEELFDHIVS CISDFLDYMG IKGPRMPLGF
TFSFPCQQTS LDAGILITWT KGFKATDCVG HDVVTLLRDA VKRREEFDLD VVAVVNDTVG
TMMTCAYEEP TCEVGLIVGT GSNACYMEEM KNVEMVEGNQ RQMCINMEWG AFGDNGCSDD
IRTDFDKVVD EYSLNSGNQR FENMISGIYL GEIVRNILID FTKKGFLFRG QISEPLKTRG
IFETKFLSQI ESDRLALLQV RAILQQLGLN STCDDSILVK TVCGVVSKRA AQLCGAGMAA
VVEKIRENRG LDRLNVTVGV DGTLYKLHPQ FSRIMHQTVK ELSPKCNVSF LLSEDGSGKG
AALITAVGVR LRGESAIS
