HXK2_EQUZE
ID HXK2_EQUZE Reviewed; 917 AA.
AC A2PYL7;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2007, sequence version 1.
DT 03-AUG-2022, entry version 54.
DE RecName: Full=Hexokinase-2 {ECO:0000305};
DE EC=2.7.1.1 {ECO:0000250|UniProtKB:P52789};
DE AltName: Full=Hexokinase type II {ECO:0000303|PubMed:17454005};
DE Short=HK II {ECO:0000303|PubMed:17454005};
GN Name=HK2 {ECO:0000250|UniProtKB:P52789};
OS Equus zebra (Mountain zebra).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Perissodactyla; Equidae; Equus.
OX NCBI_TaxID=9791;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Skeletal muscle;
RX PubMed=17454005; DOI=10.1080/10425170601136648;
RA Sato T., Itou T., Sato G., Kobayashi Y., Endo H., Sakai T.;
RT "Sequencing of cDNA and proximal promoter of equine hexokinase II gene.";
RL DNA Seq. 18:203-208(2007).
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). Mediates the initial step of
CC glycolysis by catalyzing phosphorylation of D-glucose to D-glucose 6-
CC phosphate. Plays a key role in maintaining the integrity of the outer
CC mitochondrial membrane by preventing the release of apoptogenic
CC molecules from the intermembrane space and subsequent apoptosis.
CC {ECO:0000250|UniProtKB:P52789}.
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:P52789};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22741;
CC Evidence={ECO:0000250|UniProtKB:P52789};
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:P27881};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16126;
CC Evidence={ECO:0000250|UniProtKB:P27881};
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:P52789};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17826;
CC Evidence={ECO:0000250|UniProtKB:P52789};
CC -!- ACTIVITY REGULATION: Hexokinase activity is specifically inhibited by
CC 2,6-disubstituted glucosamines. {ECO:0000250|UniProtKB:P52789}.
CC -!- PATHWAY: Carbohydrate metabolism; hexose metabolism.
CC {ECO:0000250|UniProtKB:P52789}.
CC -!- PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-
CC phosphate and glycerone phosphate from D-glucose: step 1/4.
CC {ECO:0000250|UniProtKB:P52789}.
CC -!- SUBUNIT: Monomer (By similarity). Interacts with TIGAR; the interaction
CC increases hexokinase activity in a hypoxia- and HIF1A-dependent manner
CC (By similarity). {ECO:0000250|UniProtKB:P19367,
CC ECO:0000250|UniProtKB:P52789}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane
CC {ECO:0000250|UniProtKB:P52789}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P52789}. Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:P52789}. Note=The mitochondrial-binding peptide
CC (MBP) region promotes association with the mitochondrial outer
CC membrane. The interaction with the mitochondrial outer membrane via the
CC mitochondrial-binding peptide (MBP) region promotes higher stability of
CC the protein. Release from the mitochondrial outer membrane into the
CC cytosol induces permeability transition pore (PTP) opening and
CC apoptosis. {ECO:0000250|UniProtKB:P52789}.
CC -!- DOMAIN: The N- and C-terminal halves of the protein contain a
CC hexokinase domain. In contrast to hexokinase-1 and -3 (HK1 and HK3,
CC respectively), both hexokinase domains display catalytic activity. The
CC region connecting the two hexokinase domains is required for the
CC catalytic activity of the N-terminal hexokinase domain. The N-terminal
CC half regulates stability of the whole enzyme.
CC {ECO:0000250|UniProtKB:P52789}.
CC -!- SIMILARITY: Belongs to the hexokinase family. {ECO:0000255|PROSITE-
CC ProRule:PRU01084, ECO:0000305}.
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DR EMBL; AB248869; BAF45851.1; -; mRNA.
DR AlphaFoldDB; A2PYL7; -.
DR SMR; A2PYL7; -.
DR UniPathway; UPA00109; UER00180.
DR UniPathway; UPA00242; -.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell.
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:0005536; F:glucose binding; IEA:InterPro.
DR GO; GO:0004396; F:hexokinase activity; ISS:UniProtKB.
DR GO; GO:0001678; P:cellular glucose homeostasis; IEA:InterPro.
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:0006096; P:glycolytic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0019318; P:hexose metabolic process; IEA:UniProtKB-UniPathway.
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; Kinase;
KW Membrane; Mitochondrion; Mitochondrion outer membrane; Nucleotide-binding;
KW Repeat; Transferase.
FT CHAIN 1..917
FT /note="Hexokinase-2"
FT /id="PRO_0000286050"
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..16
FT /note="Mitochondrial-binding peptide (MBP)"
FT /evidence="ECO:0000250|UniProtKB:P52789"
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..89
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 84..88
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P52789"
FT BINDING 155..156
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P52789"
FT BINDING 172..173
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P52789"
FT BINDING 208..209
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P52789"
FT BINDING 209
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P52789"
FT BINDING 235
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P52789"
FT BINDING 260
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P52789"
FT BINDING 291..294
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P52789"
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:P52789"
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 449
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P52789"
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:P52789"
FT BINDING 603..604
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P52789"
FT BINDING 620..621
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P52789"
FT BINDING 656..657
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P52789"
FT BINDING 657
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P52789"
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:P52789"
FT BINDING 682..683
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P52789"
FT BINDING 708
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P52789"
FT BINDING 739..742
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P52789"
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:P52789"
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:P52789"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P52789"
SQ SEQUENCE 917 AA; 102654 MW; 65C12AFAB051F95F CRC64;
MIASHLLAYF FTELNHDQVQ KVDQYLYHMR LSDETLLEIS KRFRKEMEKG LAATTHPTAS
VKMLPTFVRS TPDGTEHGEF LALDLGGTNF RVLRVRVTDN GLQKVEMENQ IYAIPEDIMQ
GSGTQLFDHI AGCLANFMDK LQIKDKKLPL GFTFSFPCIQ TKLDESFLVS WTKGFKSRGV
EGRDVVTLIR KAIQRRGDFD IDIVAMVNDT VATMMTCGYD DQNCEIGLIV GMGSNACYME
EMRYIDTVEG DEGRMCINME WGAFGDDGTL DDIRTEFDQE IDMGSLNPGQ QLFEKMISGM
YMGELVRLIL VKMAKEELLF RGKLSPELLT TGRFETKDVS EIEGEKDGIQ KAREVLVRLG
MDPTQEDCVA THRICQIVST RSASLCAATL AAVLQRIKEN KGEERLRSTI GVDGSVYKKH
PHFAKRLQKT VRRLVPNCDI RFLCSEDGSG KGAAMVTAVA YRLAYQHRAR LKTLEPLKLS
REQLLEVKRR MKVEMERGLS KETHASAPVK MLPTYVCATP DGTEKGDFLA LDLGGTNFRV
LLVRVRNGKR RGVEMHNKIY SIPQDIMHGT GDELFDHIVQ CIADFLEYMG MKGVSLPLGF
TFSFPCQQNR LDESILLKWT KGFKASGCEG EDVVTLLKEA IHRREEFDLD VVAVVNDTVG
TMMTCGYEDP HCEVGLIVGT GSNACYMEEM RNVELVEGEE GRMCVNTEWG AFGDNGCLDD
FCTEFDVAVD ELSLNPGKQR FEKMMSGMYL GEIVRNILID FTKRGLLFRG RISERLKTRG
IFETKFLSQI ESDCLALQQV RAILQHLGLE STCDDSIIVK EVCTVVAQRA AQLCGAGMAA
VVDKIRENRG LDTLKVTVGV DGTLYKLHPH FAKVMRETVK DLAPKCDVSF LESEDGSGKG
AALITAVACR IREAGQR
