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Database: UniProt/SWISS-PROT
Entry: HXK1_PONAB
LinkDB: HXK1_PONAB
Original site: HXK1_PONAB 
ID   HXK1_PONAB              Reviewed;         917 AA.
AC   Q5RC71;
DT   01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT   21-DEC-2004, sequence version 1.
DT   17-JUN-2020, entry version 73.
DE   RecName: Full=Hexokinase-1 {ECO:0000305};
DE            EC=2.7.1.1 {ECO:0000250|UniProtKB:P19367};
DE   AltName: Full=Hexokinase type I {ECO:0000250|UniProtKB:P19367};
DE            Short=HK I {ECO:0000250|UniProtKB:P19367};
GN   Name=HK1 {ECO:0000250|UniProtKB:P19367};
OS   Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Pongo.
OX   NCBI_TaxID=9601;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain cortex;
RG   The German cDNA consortium;
RL   Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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}.
DR   EMBL; CR858409; CAH90636.1; -; mRNA.
DR   RefSeq; NP_001125344.1; NM_001131872.1.
DR   SMR; Q5RC71; -.
DR   STRING; 9601.ENSPPYP00000002765; -.
DR   PRIDE; Q5RC71; -.
DR   GeneID; 100172246; -.
DR   KEGG; pon:100172246; -.
DR   CTD; 3098; -.
DR   eggNOG; KOG1369; Eukaryota.
DR   eggNOG; COG5026; LUCA.
DR   InParanoid; Q5RC71; -.
DR   KO; K00844; -.
DR   OrthoDB; 1153545at2759; -.
DR   UniPathway; UPA00109; UER00180.
DR   UniPathway; UPA00242; -.
DR   Proteomes; UP000001595; Unplaced.
DR   GO; GO:0005623; C:cell; IEA:GOC.
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:0019158; F:mannokinase 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: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..917
FT                   /note="Hexokinase-1"
FT                   /id="PRO_0000286047"
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   NP_BIND         84..89
FT                   /note="ATP 1"
FT                   /evidence="ECO:0000250|UniProtKB:P19367"
FT   NP_BIND         425..426
FT                   /note="ATP 1"
FT                   /evidence="ECO:0000250|UniProtKB:P19367"
FT   NP_BIND         532..537
FT                   /note="ATP 2"
FT                   /evidence="ECO:0000250|UniProtKB:P19367"
FT   NP_BIND         747..748
FT                   /note="ATP 2"
FT                   /evidence="ECO:0000250|UniProtKB:P19367"
FT   NP_BIND         784..788
FT                   /note="ATP 2"
FT                   /evidence="ECO:0000250|UniProtKB:P19367"
FT   NP_BIND         863..867
FT                   /note="ATP 2"
FT                   /evidence="ECO:0000250|UniProtKB:P19367"
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          84..91
FT                   /note="Glucose-6-phosphate 1 binding"
FT                   /evidence="ECO:0000250|UniProtKB:P19367"
FT   REGION          172..173
FT                   /note="Substrate 1 binding"
FT                   /evidence="ECO:0000250|UniProtKB:P19367"
FT   REGION          208..447
FT                   /note="Hexokinase large subdomain 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT   REGION          208..209
FT                   /note="Substrate 1 binding"
FT                   /evidence="ECO:0000250|UniProtKB:P19367"
FT   REGION          291..294
FT                   /note="Substrate 1 binding"
FT                   /evidence="ECO:0000250|UniProtKB:P19367"
FT   REGION          413..415
FT                   /note="Glucose-6-phosphate 1 binding"
FT                   /evidence="ECO:0000250|UniProtKB:P19367"
FT   REGION          521..655
FT                   /note="Hexokinase small subdomain 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT   REGION          532..536
FT                   /note="Glucose-6-phosphate 2 binding"
FT                   /evidence="ECO:0000250|UniProtKB:P19367"
FT   REGION          603..604
FT                   /note="Substrate 2 binding"
FT                   /evidence="ECO:0000250|UniProtKB:P19367"
FT   REGION          620..621
FT                   /note="Substrate 2 binding"
FT                   /evidence="ECO:0000250|UniProtKB:P19367"
FT   REGION          656..895
FT                   /note="Hexokinase large subdomain 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT   REGION          656..657
FT                   /note="Substrate 2 binding"
FT                   /evidence="ECO:0000250|UniProtKB:P19367"
FT   REGION          682..683
FT                   /note="Substrate 2 binding"
FT                   /evidence="ECO:0000250|UniProtKB:P19367"
FT   REGION          861..863
FT                   /note="Glucose-6-phosphate 2 binding"
FT                   /evidence="ECO:0000250|UniProtKB:P19367"
FT   BINDING         30
FT                   /note="ATP 1"
FT                   /evidence="ECO:0000250|UniProtKB:P19367"
FT   BINDING         155
FT                   /note="Substrate 1"
FT                   /evidence="ECO:0000250|UniProtKB:P19367"
FT   BINDING         209
FT                   /note="Glucose-6-phosphate 1"
FT                   /evidence="ECO:0000250|UniProtKB:P19367"
FT   BINDING         232
FT                   /note="Glucose-6-phosphate 1"
FT                   /evidence="ECO:0000250|UniProtKB:P19367"
FT   BINDING         235
FT                   /note="Substrate 1"
FT                   /evidence="ECO:0000250|UniProtKB:P19367"
FT   BINDING         260
FT                   /note="Substrate 1"
FT                   /evidence="ECO:0000250|UniProtKB:P19367"
FT   BINDING         345
FT                   /note="ATP 1"
FT                   /evidence="ECO:0000250|UniProtKB:P19367"
FT   BINDING         449
FT                   /note="Glucose-6-phosphate 1"
FT                   /evidence="ECO:0000250|UniProtKB:P19367"
FT   BINDING         657
FT                   /note="Glucose-6-phosphate 2"
FT                   /evidence="ECO:0000250|UniProtKB:P19367"
FT   BINDING         680
FT                   /note="ATP 2"
FT                   /evidence="ECO:0000250|UniProtKB:P19367"
FT   BINDING         680
FT                   /note="Glucose-6-phosphate 2"
FT                   /evidence="ECO:0000250|UniProtKB:P19367"
FT   BINDING         708
FT                   /note="Substrate 2"
FT                   /evidence="ECO:0000250|UniProtKB:P19367"
FT   BINDING         742
FT                   /note="Substrate 2"
FT                   /evidence="ECO:0000250|UniProtKB:P19367"
FT   BINDING         897
FT                   /note="Glucose-6-phosphate 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   917 AA;  102363 MW;  BCB4765425999C79 CRC64;
     MIAAQLLAYY FTELKDDQVK KIDKYLYAMR LSDETLIDIM TRFRKEMKNG LSRDFNPTAT
     VKMLPTFVRS IPDGSEKGDF IALDLGGSSF RILRVQVNHE KNQNVHMESE VYDTPENIVH
     GSGSQLFDHV AECLGDFMEK RKIKDKKSPV GFTFSFPCQQ SKIDEAVLIT WTKRFKASGV
     EGADVVKLLN KAIKKRGDYD ANIVAVVNDT VGTMMTCGYD DQHCEVGLII GTGTNACYME
     ELRHIDLVEG DEGRMCINTE WGAFGDDGSL EDIRTEFDRE IDRGSLNPGK QLFEKMVSGM
     YLGELVRLIL VKMAKEGLLF EGRITPELLT RGKFNTSDVS AIEKNKEGLH NAKEILTRLG
     VEPSDDDCVS VQHVCTIVSF RSANLVAATL GAILNRLRDN KGTPRLRTTV GVDGSLYKTH
     PQYSRRFHKT LRRLVPDSDV RFLLSESGSG KGAAMVTAVA YRLAEQHRQI EETLAHFHLT
     KDMLLEVKKR MRAEMELGLR KQTHNNAAVK MLPSFVRRTP DGTENGDFLA LDLGGTNFRV
     LLVKIRSGKK RTVEMHNKIY AIPIEIMQGT GEELFDHIVS CISDFLDYMG IKGPRMPLGF
     TFSFPCKQTS LDAGILITWT KGFKATDCVG NDVATLLRDA IKRREEFDLD VVAVVNDTVG
     TMMTCAYEEP TCEVGLIVGT GSNACYMEEM KNVEMVEGDQ GQMCINMEWG AFGDNGCLDD
     IRTHYDRLVD EYSLNAGKQR YEKMISGMYL GEIVRNILID FTKKGFLFRG QISEPLKTRG
     IFETKFLSQI ESDRLALLQV RAILQQLGLN STCDDSILVK TVCGVVSRRA AQLCGAGMAA
     VVDKIRENRG LDRLNVTVGV DGTLYKLHPH FSRIMHQTVK ELSPKCNVSF LLSEDGSGKG
     AALITAVGVR LRTEASS
//
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