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Protein

Glucokinase

Gene

Gck

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

Miscellaneous

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

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)DescriptionActionsGraphical viewLength
Binding sitei104ATPSequence analysis1
Binding sitei228ATPBy similarity1
Binding sitei231SubstrateBy similarity1
Binding sitei256SubstrateBy similarity1
Binding sitei290SubstrateBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi78 – 83ATPSequence analysis6
Nucleotide bindingi295 – 296ATPBy similarity2
Nucleotide bindingi332 – 336ATPBy similarity5
Nucleotide bindingi411 – 415ATPBy similarity5

GO - Molecular functioni

  • ATP binding Source: UniProtKB
  • glucokinase activity Source: MGI
  • glucose binding Source: UniProtKB
  • hexokinase activity Source: CACAO

GO - Biological processi

  • calcium ion import Source: UniProtKB
  • carbohydrate phosphorylation Source: MGI
  • cellular glucose homeostasis Source: MGI
  • detection of glucose Source: UniProtKB
  • endocrine pancreas development Source: Reactome
  • glucose homeostasis Source: UniProtKB
  • glucose metabolic process Source: MGI
  • glycolytic process Source: GO_Central
  • NADP metabolic process Source: MGI
  • negative regulation of gluconeogenesis Source: UniProtKB
  • positive regulation of glycogen biosynthetic process Source: UniProtKB
  • positive regulation of insulin secretion Source: UniProtKB
  • regulation of insulin secretion Source: MGI
  • regulation of potassium ion transport Source: MGI

Keywordsi

Molecular functionKinase, Transferase
Biological processGlycolysis
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-170822. Regulation of Glucokinase by Glucokinase Regulatory Protein.
R-MMU-210745. Regulation of gene expression in beta cells.
R-MMU-70171. Glycolysis.
SABIO-RKiP52792.

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:1270854. Gck.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL3112387.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001975941 – 465GlucokinaseAdd BLAST465

Proteomic databases

PaxDbiP52792.
PRIDEiP52792.

PTM databases

iPTMnetiP52792.
PhosphoSitePlusiP52792.
SwissPalmiP52792.

Expressioni

Tissue specificityi

Isoform 1: Pancreas, anterior pituitary. Isoform 2: Liver.

Inductioni

Up-regulated by endocannabinoid anandamide/AEA.1 Publication

Gene expression databases

BgeeiENSMUSG00000041798.
CleanExiMM_GCK.
ExpressionAtlasiP52792. baseline and differential.
GenevisibleiP52792. MM.

Interactioni

Subunit structurei

Monomer. Interacts with MIDN; the interaction occurs preferentially at low glucose levels and results in inhibition of GCK activity.By similarity

Protein-protein interaction databases

BioGridi222262. 4 interactors.
CORUMiP52792.
STRINGi10090.ENSMUSP00000099984.

Chemistry databases

BindingDBiP52792.

Structurei

3D structure databases

ProteinModelPortaliP52792.
SMRiP52792.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini10 – 454HexokinasePROSITE-ProRule annotationAdd BLAST445

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni67 – 203Hexokinase small subdomainPROSITE-ProRule annotationAdd BLAST137
Regioni151 – 152Substrate bindingBy similarity2
Regioni168 – 169Substrate bindingBy similarity2
Regioni204 – 443Hexokinase large subdomainPROSITE-ProRule annotationAdd BLAST240
Regioni204 – 205Substrate bindingBy similarity2

Sequence similaritiesi

Belongs to the hexokinase family.PROSITE-ProRule annotationCurated

Phylogenomic databases

eggNOGiKOG1369. Eukaryota.
COG5026. LUCA.
GeneTreeiENSGT00390000017159.
HOGENOMiHOG000162670.
HOVERGENiHBG000142.
InParanoidiP52792.
KOiK12407.
OMAiERQFFRA.
OrthoDBiEOG091G08MD.
PhylomeDBiP52792.
TreeFamiTF314238.

Family and domain databases

InterProiView protein in InterPro
IPR001312. Hexokinase.
IPR019807. Hexokinase_BS.
IPR022673. Hexokinase_C.
IPR022672. Hexokinase_N.
PANTHERiPTHR19443. PTHR19443. 1 hit.
PfamiView protein in Pfam
PF00349. Hexokinase_1. 1 hit.
PF03727. Hexokinase_2. 1 hit.
PROSITEiView protein in PROSITE
PS00378. HEXOKINASE_1. 1 hit.
PS51748. HEXOKINASE_2. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative promoter usage and alternative splicing. AlignAdd to basket

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)DescriptionActionsGraphical viewLength
Sequence conflicti133F → L in AAA37703 (PubMed:1999433).Curated1
Sequence conflicti159I → L in AAA37703 (PubMed:1999433).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0020761 – 15MLDDR…TKKEK → MAVDTTRRGAQSLTL in isoform 2. 1 PublicationAdd BLAST15

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.2. mouse. [P52792-1]

Keywords - Coding sequence diversityi

Alternative promoter usage, Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiHXK4_MOUSE
AccessioniPrimary (citable) accession number: P52792
Secondary accession number(s): P52791
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: September 27, 2017
This is version 149 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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