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P17712

- HXK4_RAT

UniProt

P17712 - HXK4_RAT

Protein

Glucokinase

Gene

Gck

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 123 (01 Oct 2014)
      Sequence version 2 (01 Nov 1990)
      Previous versions | rss
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    Functioni

    Catalyzes the initial step in utilization of glucose by the beta-cell and liver at physiological glucose concentration. Pancreatic glucokinase plays an important role in modulating insulin secretion. Hepatic glucokinase helps to facilitate the uptake and conversion of glucose by acting as an insulin-sensitive determinant of hepatic glucose usage.

    Catalytic activityi

    ATP + D-glucose = ADP + D-glucose 6-phosphate.

    Enzyme regulationi

    Low glucose and high fructose-6-phosphate triggers association with the inhibitor GKRP followed by sequestration in the nucleus.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei104 – 1041ATPSequence Analysis
    Binding sitei228 – 2281ATPBy similarity
    Binding sitei231 – 2311SubstrateBy similarity
    Binding sitei256 – 2561SubstrateBy similarity
    Binding sitei290 – 2901SubstrateBy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi78 – 836ATPSequence Analysis
    Nucleotide bindingi295 – 2962ATPBy similarity
    Nucleotide bindingi332 – 3365ATPBy similarity
    Nucleotide bindingi411 – 4155ATPBy similarity

    GO - Molecular functioni

    1. ADP binding Source: RGD
    2. ATP binding Source: UniProtKB
    3. glucokinase activity Source: UniProtKB
    4. glucose binding Source: UniProtKB
    5. magnesium ion binding Source: RGD
    6. protein binding Source: BHF-UCL
    7. protein phosphatase binding Source: RGD

    GO - Biological processi

    1. calcium ion import Source: Ensembl
    2. carbohydrate phosphorylation Source: RGD
    3. cellular glucose homeostasis Source: RGD
    4. cellular response to glucose starvation Source: RGD
    5. cellular response to insulin stimulus Source: BHF-UCL
    6. cellular response to leptin stimulus Source: BHF-UCL
    7. detection of glucose Source: UniProtKB
    8. fructose 2,6-bisphosphate metabolic process Source: RGD
    9. glucose 6-phosphate metabolic process Source: RGD
    10. glucose homeostasis Source: UniProtKB
    11. glucose metabolic process Source: RGD
    12. glycogen biosynthetic process Source: RGD
    13. glycolytic process Source: RGD
    14. lipid homeostasis Source: RGD
    15. NADP metabolic process Source: Ensembl
    16. negative regulation of epinephrine secretion Source: RGD
    17. negative regulation of gluconeogenesis Source: UniProtKB
    18. positive regulation of cytosolic calcium ion concentration Source: RGD
    19. positive regulation of glycogen biosynthetic process Source: UniProtKB
    20. positive regulation of glycolytic process Source: RGD
    21. positive regulation of insulin secretion Source: UniProtKB
    22. positive regulation of phosphorylation Source: RGD
    23. regulation of potassium ion transport Source: Ensembl
    24. response to glucose Source: RGD
    25. second-messenger-mediated signaling Source: RGD

    Keywords - Molecular functioni

    Kinase, Transferase

    Keywords - Biological processi

    Glycolysis

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    ReactomeiREACT_205960. Glucose transport.
    SABIO-RKP17712.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Glucokinase (EC:2.7.1.2)
    Alternative name(s):
    Hexokinase type IV
    Short name:
    HK IV
    Hexokinase-4
    Short name:
    HK4
    Hexokinase-D
    Gene namesi
    Name:Gck
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Chromosome 14

    Organism-specific databases

    RGDi2670. Gck.

    Subcellular locationi

    Cytoplasm 1 Publication. Nucleus 1 Publication
    Note: Under low glucose concentrations, GCK associates with GKRP and the inactive complex is recruited to the hepatocyte nucleus.

    GO - Cellular componenti

    1. basal cortex Source: RGD
    2. cell cortex Source: RGD
    3. cytoplasm Source: BHF-UCL
    4. cytosol Source: RGD
    5. mitochondrion Source: RGD
    6. nucleoplasm Source: RGD
    7. nucleus Source: BHF-UCL
    8. secretory granule Source: RGD

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 465465GlucokinasePRO_0000197595Add
    BLAST

    Proteomic databases

    PRIDEiP17712.

    Expressioni

    Tissue specificityi

    Pancreas (isoform 1 and isoform 2) and liver (isoform 3).

    Gene expression databases

    GenevestigatoriP17712.

    Interactioni

    Subunit structurei

    Monomer.By similarity

    Protein-protein interaction databases

    IntActiP17712. 2 interactions.
    MINTiMINT-1795103.

    Structurei

    3D structure databases

    ProteinModelPortaliP17712.
    SMRiP17712. Positions 16-461.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini12 – 217206Hexokinase type-1Add
    BLAST
    Domaini219 – 458240Hexokinase type-2Add
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni151 – 1522Substrate bindingBy similarity
    Regioni168 – 1692Substrate bindingBy similarity
    Regioni204 – 2052Substrate bindingBy similarity

    Sequence similaritiesi

    Belongs to the hexokinase family.Curated
    Contains 1 hexokinase type-1 domain.Curated
    Contains 1 hexokinase type-2 domain.Curated

    Phylogenomic databases

    eggNOGiCOG5026.
    GeneTreeiENSGT00390000017159.
    HOGENOMiHOG000162670.
    HOVERGENiHBG000142.
    KOiK12407.
    OMAiRCEITFL.
    OrthoDBiEOG7S21X5.
    PhylomeDBiP17712.

    Family and domain databases

    InterProiIPR001312. Hexokinase.
    IPR022673. Hexokinase_C.
    IPR019807. Hexokinase_CS.
    IPR022672. Hexokinase_N.
    [Graphical view]
    PANTHERiPTHR19443. PTHR19443. 1 hit.
    PfamiPF00349. Hexokinase_1. 1 hit.
    PF03727. Hexokinase_2. 1 hit.
    [Graphical view]
    PRINTSiPR00475. HEXOKINASE.
    PROSITEiPS00378. HEXOKINASES. 1 hit.
    [Graphical view]

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative promoter usage and alternative splicing. Align

    Note: A number of isoforms are produced by alternative promoter usage. The use of alternative promoters apparently enables the type IV hexokinase gene to be regulated by insulin in the liver and glucose in the beta cell. This may constitute an important feedback loop for maintaining glucose homeostasis.

    Isoform 1 (identifier: P17712-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MLDDRARMEA TKKEKVEQIL AEFQLQEEDL KKVMSRMQKE MDRGLRLETH    50
    EEASVKMLPT YVRSTPEGSE VGDFLSLDLG GTNFRVMLVK VGEGEAGQWS 100
    VKTKHQMYSI PEDAMTGTAE MLFDYISECI SDFLDKHQMK HKKLPLGFTF 150
    SFPVRHEDLD KGILLNWTKG FKASGAEGNN IVGLLRDAIK RRGDFEMDVV 200
    AMVNDTVATM ISCYYEDRQC EVGMIVGTGC NACYMEEMQN VELVEGDEGR 250
    MCVNTEWGAF GDSGELDEFL LEYDRMVDES SANPGQQLYE KIIGGKYMGE 300
    LVRLVLLKLV DENLLFHGEA SEQLRTRGAF ETRFVSQVES DSGDRKQIHN 350
    ILSTLGLRPS VTDCDIVRRA CESVSTRAAH MCSAGLAGVI NRMRESRSED 400
    VMRITVGVDG SVYKLHPSFK ERFHASVRRL TPNCEITFIE SEEGSGRGAA 450
    LVSAVACKKA CMLAQ 465
    Length:465
    Mass (Da):52,116
    Last modified:November 1, 1990 - v2
    Checksum:i65B36673DF9297BE
    GO
    Isoform 2 (identifier: P17712-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         122-138: Missing.

    Show »
    Length:448
    Mass (Da):50,061
    Checksum:i4925A5DD0CA2668B
    GO
    Isoform 3 (identifier: P17712-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-15: MLDDRARMEATKKEK → MAMDTTRCGAQLLTL

    Show »
    Length:465
    Mass (Da):51,919
    Checksum:i7495EE087FE4F8C7
    GO

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 1515MLDDR…TKKEK → MAMDTTRCGAQLLTL in isoform 3. 1 PublicationVSP_002077Add
    BLAST
    Alternative sequencei122 – 13817Missing in isoform 2. CuratedVSP_002078Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    J04218 mRNA. Translation: AAA41229.1.
    M24952
    , M24943, M24944, M24945, M24947, M24948, M24949, M24950, M24951 Genomic DNA. Translation: AAA41230.1.
    M25806 Genomic DNA. Translation: AAA41238.1.
    M25807 mRNA. Translation: AAA41239.1.
    M58759 mRNA. Translation: AAA41236.1.
    X53588 mRNA. Translation: CAA37657.1.
    X53590 Genomic DNA. Translation: CAA37660.1.
    M30770 Genomic DNA. Translation: AAA41231.1.
    PIRiA31810.
    I84740.
    RefSeqiNP_001257779.1. NM_001270850.1. [P17712-2]
    NP_036697.1. NM_012565.2. [P17712-3]
    XP_006251241.1. XM_006251179.1. [P17712-1]
    UniGeneiRn.10447.

    Genome annotation databases

    EnsembliENSRNOT00000019625; ENSRNOP00000019625; ENSRNOG00000014447. [P17712-3]
    GeneIDi24385.
    KEGGirno:24385.
    UCSCiRGD:2670. rat. [P17712-1]

    Keywords - Coding sequence diversityi

    Alternative promoter usage, Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    J04218 mRNA. Translation: AAA41229.1 .
    M24952
    , M24943 , M24944 , M24945 , M24947 , M24948 , M24949 , M24950 , M24951 Genomic DNA. Translation: AAA41230.1 .
    M25806 Genomic DNA. Translation: AAA41238.1 .
    M25807 mRNA. Translation: AAA41239.1 .
    M58759 mRNA. Translation: AAA41236.1 .
    X53588 mRNA. Translation: CAA37657.1 .
    X53590 Genomic DNA. Translation: CAA37660.1 .
    M30770 Genomic DNA. Translation: AAA41231.1 .
    PIRi A31810.
    I84740.
    RefSeqi NP_001257779.1. NM_001270850.1. [P17712-2 ]
    NP_036697.1. NM_012565.2. [P17712-3 ]
    XP_006251241.1. XM_006251179.1. [P17712-1 ]
    UniGenei Rn.10447.

    3D structure databases

    ProteinModelPortali P17712.
    SMRi P17712. Positions 16-461.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi P17712. 2 interactions.
    MINTi MINT-1795103.

    Chemistry

    BindingDBi P17712.
    ChEMBLi CHEMBL3882.

    Proteomic databases

    PRIDEi P17712.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSRNOT00000019625 ; ENSRNOP00000019625 ; ENSRNOG00000014447 . [P17712-3 ]
    GeneIDi 24385.
    KEGGi rno:24385.
    UCSCi RGD:2670. rat. [P17712-1 ]

    Organism-specific databases

    CTDi 2645.
    RGDi 2670. Gck.

    Phylogenomic databases

    eggNOGi COG5026.
    GeneTreei ENSGT00390000017159.
    HOGENOMi HOG000162670.
    HOVERGENi HBG000142.
    KOi K12407.
    OMAi RCEITFL.
    OrthoDBi EOG7S21X5.
    PhylomeDBi P17712.

    Enzyme and pathway databases

    Reactomei REACT_205960. Glucose transport.
    SABIO-RK P17712.

    Miscellaneous databases

    NextBioi 603157.

    Gene expression databases

    Genevestigatori P17712.

    Family and domain databases

    InterProi IPR001312. Hexokinase.
    IPR022673. Hexokinase_C.
    IPR019807. Hexokinase_CS.
    IPR022672. Hexokinase_N.
    [Graphical view ]
    PANTHERi PTHR19443. PTHR19443. 1 hit.
    Pfami PF00349. Hexokinase_1. 1 hit.
    PF03727. Hexokinase_2. 1 hit.
    [Graphical view ]
    PRINTSi PR00475. HEXOKINASE.
    PROSITEi PS00378. HEXOKINASES. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "The amino acid sequence of rat liver glucokinase deduced from cloned cDNA."
      Andreone T.L., Printz R.L., Pilkis S.J., Magnuson M.A., Granner D.K.
      J. Biol. Chem. 264:363-369(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), PARTIAL PROTEIN SEQUENCE.
      Tissue: Liver.
    2. "Alternative splicing of glucokinase mRNA in rat liver."
      Hayzer D.J., Iynedjian P.B.
      Biochem. J. 270:261-263(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], ALTERNATIVE SPLICING.
      Tissue: Liver.
    3. "An alternate promoter in the glucokinase gene is active in the pancreatic beta cell."
      Magnuson M.A., Shelton K.D.
      J. Biol. Chem. 264:15936-15942(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 1-15 (ISOFORM 1).
      Tissue: Pancreas.
    4. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-15 (ISOFORM 3).
    5. Cited for: NUCLEOTIDE SEQUENCE OF 1-15 (ISOFORM 3).
    6. "Expression of normal and novel glucokinase mRNAs in anterior pituitary and islet cells."
      Hughes S.D., Quaade C., Milburn J.L., Cassidy L., Newgard C.B.
      J. Biol. Chem. 266:4521-4530(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-166 (ISOFORM 1).
    7. "Glucokinase regulatory protein is essential for the proper subcellular localisation of liver glucokinase."
      de la Iglesia N., Veiga-da-Cunha M., Van Schaftingen E., Guinovart J.J., Ferrer J.C.
      FEBS Lett. 456:332-338(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: ENZYME REGULATION, SUBCELLULAR LOCATION.

    Entry informationi

    Entry nameiHXK4_RAT
    AccessioniPrimary (citable) accession number: P17712
    Secondary accession number(s): P17711
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1990
    Last sequence update: November 1, 1990
    Last modified: October 1, 2014
    This is version 123 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    In vertebrates there are four major glucose-phosphorylating isoenzymes, designated hexokinase I, II, III and IV (glucokinase).

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3