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P52792

- HXK4_MOUSE

UniProt

P52792 - HXK4_MOUSE

Protein

Glucokinase

Gene

Gck

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 121 (01 Oct 2014)
      Sequence version 1 (01 Oct 1996)
      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.By similarity

    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: Ensembl
    2. ATP binding Source: UniProtKB
    3. glucokinase activity Source: UniProtKB
    4. glucose binding Source: UniProtKB
    5. magnesium ion binding Source: Ensembl
    6. protein binding Source: UniProtKB

    GO - Biological processi

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

    Keywords - Molecular functioni

    Kinase, Transferase

    Keywords - Biological processi

    Glycolysis

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    ReactomeiREACT_204192. Regulation of Glucokinase by Glucokinase Regulatory Protein.
    REACT_214529. Regulation of gene expression in beta cells.
    SABIO-RKP52792.

    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
    Synonyms:Gk
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 11

    Organism-specific databases

    MGIiMGI:1270854. Gck.

    Subcellular locationi

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

    GO - Cellular componenti

    1. cell cortex Source: Ensembl
    2. cytosol Source: MGI
    3. mitochondrion Source: MGI
    4. nucleoplasm Source: Ensembl
    5. nucleus Source: BHF-UCL
    6. secretory granule Source: Ensembl

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 465465GlucokinasePRO_0000197594Add
    BLAST

    Proteomic databases

    MaxQBiP52792.
    PaxDbiP52792.
    PRIDEiP52792.

    PTM databases

    PhosphoSiteiP52792.

    Expressioni

    Tissue specificityi

    Pancreas, anterior pituitary (isoform 1) and liver (isoform 2).

    Gene expression databases

    ArrayExpressiP52792.
    BgeeiP52792.
    CleanExiMM_GCK.
    GenevestigatoriP52792.

    Interactioni

    Subunit structurei

    Monomer.By similarity

    Protein-protein interaction databases

    BioGridi222262. 3 interactions.

    Structurei

    3D structure databases

    ProteinModelPortaliP52792.
    SMRiP52792. Positions 16-460.
    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.
    HOGENOMiHOG000162670.
    HOVERGENiHBG000142.
    KOiK12407.
    OMAiRCEITFL.
    OrthoDBiEOG7S21X5.
    PhylomeDBiP52792.
    TreeFamiTF314238.

    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 (2)i

    Sequence statusi: Complete.

    This entry describes 2 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: P52792-1) [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 MDRGLKLETH    50
    QEASVKMLPT YVRSTPEGSE VGDFLSLDLG GTNFRVMLVK VGEGEAGQWS 100
    VKTKHQMYSI PEDAMTGTAE MLFDYISECI SDFLDKHQMK HKKLPLGFTF 150
    SFPVRHEDID KGILLNWTKG FKASGAEGNN IVGLLRDAIK RRGDFEMDVV 200
    AMVNDTVATM ISCYYEDRQC EVGMIVGTGC NACYMEEMQN VELVEGDEGR 250
    MCVNTEWGAF GNSGELDEFL LEYDRMVDES SVNPGQQLYE KIIGGKYMGE 300
    LVRLVLLKLV EENLLFHGEA SEQLRTRGAF ETRFVSQVES DSGDRRQILN 350
    ILSTLGLRPS VADCDIVRRA CESVSTRAAH MCSAGLAGVI NRMRESRSED 400
    VMRITVGVDG SVYKLHPSFK ERFHASVRRL TPNCEITFIE SEEGSGRGAA 450
    LVSAVACKKA CMLGQ 465
    Length:465
    Mass (Da):52,089
    Last modified:October 1, 1996 - v1
    Checksum:i8C85EED079A52D61
    GO
    Isoform 2 (identifier: P52792-2) [UniParc]FASTAAdd to Basket

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

    Show »
    Length:465
    Mass (Da):51,886
    Checksum:iDAC911920818B811
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti133 – 1331F → L in AAA37703. (PubMed:1999433)Curated
    Sequence conflicti159 – 1591I → L in AAA37703. (PubMed:1999433)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 1515MLDDR…TKKEK → MAVDTTRRGAQSLTL in isoform 2. 1 PublicationVSP_002076Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L38990 mRNA. Translation: AAB00360.1.
    L41631 Genomic DNA. Translation: AAC42074.1.
    BC011139 mRNA. Translation: AAH11139.1.
    M58755 mRNA. Translation: AAA37703.1.
    CCDSiCCDS24409.1. [P52792-1]
    CCDS70135.1. [P52792-2]
    PIRiI49693.
    I49694.
    RefSeqiNP_001274315.1. NM_001287386.1. [P52792-2]
    NP_034422.2. NM_010292.5. [P52792-1]
    UniGeneiMm.220358.

    Genome annotation databases

    EnsembliENSMUST00000102920; ENSMUSP00000099984; ENSMUSG00000041798. [P52792-1]
    ENSMUST00000109822; ENSMUSP00000105447; ENSMUSG00000041798. [P52792-2]
    ENSMUST00000109823; ENSMUSP00000105448; ENSMUSG00000041798. [P52792-2]
    GeneIDi103988.
    KEGGimmu:103988.
    UCSCiuc007hxn.1. mouse. [P52792-1]

    Keywords - Coding sequence diversityi

    Alternative promoter usage, Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L38990 mRNA. Translation: AAB00360.1 .
    L41631 Genomic DNA. Translation: AAC42074.1 .
    BC011139 mRNA. Translation: AAH11139.1 .
    M58755 mRNA. Translation: AAA37703.1 .
    CCDSi CCDS24409.1. [P52792-1 ]
    CCDS70135.1. [P52792-2 ]
    PIRi I49693.
    I49694.
    RefSeqi NP_001274315.1. NM_001287386.1. [P52792-2 ]
    NP_034422.2. NM_010292.5. [P52792-1 ]
    UniGenei Mm.220358.

    3D structure databases

    ProteinModelPortali P52792.
    SMRi P52792. Positions 16-460.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 222262. 3 interactions.

    PTM databases

    PhosphoSitei P52792.

    Proteomic databases

    MaxQBi P52792.
    PaxDbi P52792.
    PRIDEi P52792.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000102920 ; ENSMUSP00000099984 ; ENSMUSG00000041798 . [P52792-1 ]
    ENSMUST00000109822 ; ENSMUSP00000105447 ; ENSMUSG00000041798 . [P52792-2 ]
    ENSMUST00000109823 ; ENSMUSP00000105448 ; ENSMUSG00000041798 . [P52792-2 ]
    GeneIDi 103988.
    KEGGi mmu:103988.
    UCSCi uc007hxn.1. mouse. [P52792-1 ]

    Organism-specific databases

    CTDi 2645.
    MGIi MGI:1270854. Gck.

    Phylogenomic databases

    eggNOGi COG5026.
    HOGENOMi HOG000162670.
    HOVERGENi HBG000142.
    KOi K12407.
    OMAi RCEITFL.
    OrthoDBi EOG7S21X5.
    PhylomeDBi P52792.
    TreeFami TF314238.

    Enzyme and pathway databases

    Reactomei REACT_204192. Regulation of Glucokinase by Glucokinase Regulatory Protein.
    REACT_214529. Regulation of gene expression in beta cells.
    SABIO-RK P52792.

    Miscellaneous databases

    NextBioi 356305.
    PROi P52792.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P52792.
    Bgeei P52792.
    CleanExi MM_GCK.
    Genevestigatori P52792.

    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. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    2. "Cloning and characterization of the mouse glucokinase gene locus and identification of distal liver-specific DNase I hypersensitive sites."
      Postic C., Niswender K.D., Decaux J.F., Shelton K.D., Gouhot B., Petterpher C.C., Granner D.K., Girard J., Magnuson M.A.
      Genomics 29:740-750(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2).
      Strain: 129/Sv.
      Tissue: Liver.
    3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
      Strain: FVB/N.
      Tissue: Liver.
    4. "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).
      Tissue: Pancreas.

    Entry informationi

    Entry nameiHXK4_MOUSE
    AccessioniPrimary (citable) accession number: P52792
    Secondary accession number(s): P52791
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1996
    Last sequence update: October 1, 1996
    Last modified: October 1, 2014
    This is version 121 of the entry and version 1 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, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3