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Protein

Glucokinase

Gene

Gck

Organism
Rattus norvegicus (Rat)
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.By similarity

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.By similarity

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)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

  • ADP binding Source: RGD
  • ATP binding Source: RGD
  • glucokinase activity Source: RGD
  • glucose binding Source: RGD
  • hexokinase activity Source: RGD
  • magnesium ion binding Source: RGD
  • protein phosphatase binding Source: RGD

GO - Biological processi

  • calcium ion import Source: RGD
  • carbohydrate phosphorylation Source: RGD
  • cellular glucose homeostasis Source: RGD
  • cellular response to glucose starvation Source: RGD
  • cellular response to insulin stimulus Source: BHF-UCL
  • cellular response to leptin stimulus Source: BHF-UCL
  • detection of glucose Source: BHF-UCL
  • fructose 2,6-bisphosphate metabolic process Source: RGD
  • glucose 6-phosphate metabolic process Source: RGD
  • glucose homeostasis Source: RGD
  • glucose metabolic process Source: RGD
  • glycogen biosynthetic process Source: RGD
  • glycolytic process Source: RGD
  • lipid homeostasis Source: RGD
  • NADP metabolic process Source: RGD
  • negative regulation of epinephrine secretion Source: RGD
  • negative regulation of gluconeogenesis Source: UniProtKB
  • positive regulation of cytosolic calcium ion concentration Source: RGD
  • positive regulation of glycogen biosynthetic process Source: UniProtKB
  • positive regulation of glycolytic process Source: RGD
  • positive regulation of insulin secretion Source: RGD
  • positive regulation of phosphorylation Source: RGD
  • regulation of insulin secretion Source: RGD
  • regulation of potassium ion transport Source: RGD
  • response to glucose Source: RGD
  • second-messenger-mediated signaling Source: RGD

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-RNO-170822. Regulation of Glucokinase by Glucokinase Regulatory Protein.
R-RNO-70171. Glycolysis.
SABIO-RKiP17712.

Names & Taxonomyi

Protein namesi
Recommended name:
Glucokinase (EC:2.7.1.2By similarity)
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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 14

Organism-specific databases

RGDi2670. 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

ChEMBLiCHEMBL3882.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001975951 – 465GlucokinaseAdd BLAST465

Proteomic databases

PaxDbiP17712.
PRIDEiP17712.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSRNOG00000061527.
ExpressionAtlasiP17712. differential.

Interactioni

Subunit structurei

Monomer (By similarity). Interacts with MIDN; the interaction occurs preferentially at low glucose levels and results in inhibition of GCK activity (PubMed:24187134).By similarity1 Publication

GO - Molecular functioni

  • protein phosphatase binding Source: RGD

Protein-protein interaction databases

IntActiP17712. 2 interactors.
MINTiMINT-1795103.
STRINGi10116.ENSRNOP00000019625.

Chemistry databases

BindingDBiP17712.

Structurei

3D structure databases

ProteinModelPortaliP17712.
SMRiP17712.
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.
InParanoidiP17712.
KOiK12407.
PhylomeDBiP17712.

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 (3)i

Sequence statusi: Complete.

This entry describes 3 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: 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

        10         20         30         40         50
MLDDRARMEA TKKEKVEQIL AEFQLQEEDL KKVMSRMQKE MDRGLRLETH
60 70 80 90 100
EEASVKMLPT YVRSTPEGSE VGDFLSLDLG GTNFRVMLVK VGEGEAGQWS
110 120 130 140 150
VKTKHQMYSI PEDAMTGTAE MLFDYISECI SDFLDKHQMK HKKLPLGFTF
160 170 180 190 200
SFPVRHEDLD KGILLNWTKG FKASGAEGNN IVGLLRDAIK RRGDFEMDVV
210 220 230 240 250
AMVNDTVATM ISCYYEDRQC EVGMIVGTGC NACYMEEMQN VELVEGDEGR
260 270 280 290 300
MCVNTEWGAF GDSGELDEFL LEYDRMVDES SANPGQQLYE KIIGGKYMGE
310 320 330 340 350
LVRLVLLKLV DENLLFHGEA SEQLRTRGAF ETRFVSQVES DSGDRKQIHN
360 370 380 390 400
ILSTLGLRPS VTDCDIVRRA CESVSTRAAH MCSAGLAGVI NRMRESRSED
410 420 430 440 450
VMRITVGVDG SVYKLHPSFK ERFHASVRRL TPNCEITFIE SEEGSGRGAA
460
LVSAVACKKA CMLAQ
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)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0020771 – 15MLDDR…TKKEK → MAMDTTRCGAQLLTL in isoform 3. 1 PublicationAdd BLAST15
Alternative sequenceiVSP_002078122 – 138Missing in isoform 2. CuratedAdd BLAST17

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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_006251179.3. [P17712-1]
UniGeneiRn.10447.

Genome annotation databases

EnsembliENSRNOT00000086343; ENSRNOP00000071435; ENSRNOG00000061527. [P17712-3]
ENSRNOT00000086474; ENSRNOP00000069954; ENSRNOG00000061527. [P17712-2]
GeneIDi24385.
KEGGirno:24385.
UCSCiRGD:2670. rat. [P17712-1]

Keywords - Coding sequence diversityi

Alternative promoter usage, Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiHXK4_RAT
AccessioniPrimary (citable) accession number: P17712
Secondary accession number(s): P17711
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: November 1, 1990
Last modified: November 22, 2017
This is version 150 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families