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P52792

- HXK4_MOUSE

UniProt

P52792 - HXK4_MOUSE

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Protein

Glucokinase

Gene

Gck

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli

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

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
Complete GO annotation...

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
Complete GO annotation...

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

BgeeiP52792.
CleanExiMM_GCK.
ExpressionAtlasiP52792. baseline and differential.
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.
InParanoidiP52792.
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

        10         20         30         40         50
MLDDRARMEA TKKEKVEQIL AEFQLQEEDL KKVMSRMQKE MDRGLKLETH
60 70 80 90 100
QEASVKMLPT YVRSTPEGSE VGDFLSLDLG GTNFRVMLVK VGEGEAGQWS
110 120 130 140 150
VKTKHQMYSI PEDAMTGTAE MLFDYISECI SDFLDKHQMK HKKLPLGFTF
160 170 180 190 200
SFPVRHEDID KGILLNWTKG FKASGAEGNN IVGLLRDAIK RRGDFEMDVV
210 220 230 240 250
AMVNDTVATM ISCYYEDRQC EVGMIVGTGC NACYMEEMQN VELVEGDEGR
260 270 280 290 300
MCVNTEWGAF GNSGELDEFL LEYDRMVDES SVNPGQQLYE KIIGGKYMGE
310 320 330 340 350
LVRLVLLKLV EENLLFHGEA SEQLRTRGAF ETRFVSQVES DSGDRRQILN
360 370 380 390 400
ILSTLGLRPS VADCDIVRRA CESVSTRAAH MCSAGLAGVI NRMRESRSED
410 420 430 440 450
VMRITVGVDG SVYKLHPSFK ERFHASVRRL TPNCEITFIE SEEGSGRGAA
460
LVSAVACKKA CMLGQ
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.

Chemistry

ChEMBLi CHEMBL3112387.

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.
InParanoidi P52792.
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

Bgeei P52792.
CleanExi MM_GCK.
ExpressionAtlasi P52792. baseline and differential.
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

« Hide 'large scale' publications
  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 29, 2014
This is version 122 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