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P52792

- HXK4_MOUSE

UniProt

P52792 - HXK4_MOUSE

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Protein
Glucokinase
Gene
Gck, Gk
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 – 1041ATP Reviewed prediction
Binding sitei228 – 2281ATP By similarity
Binding sitei231 – 2311Substrate By similarity
Binding sitei256 – 2561Substrate By similarity
Binding sitei290 – 2901Substrate By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi78 – 836ATP Reviewed prediction
Nucleotide bindingi295 – 2962ATP By similarity
Nucleotide bindingi332 – 3365ATP By similarity
Nucleotide bindingi411 – 4155ATP By 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. NADP metabolic process Source: MGI
  2. calcium ion import Source: UniProtKB
  3. carbohydrate phosphorylation Source: MGI
  4. cellular glucose homeostasis Source: MGI
  5. cellular response to glucose starvation Source: Ensembl
  6. cellular response to insulin stimulus Source: Ensembl
  7. cellular response to leptin stimulus Source: Ensembl
  8. detection of glucose Source: UniProtKB
  9. endocrine pancreas development Source: Reactome
  10. fructose 2,6-bisphosphate metabolic process Source: Ensembl
  11. glucose homeostasis Source: UniProtKB
  12. glucose metabolic process Source: MGI
  13. glycogen biosynthetic process Source: Ensembl
  14. glycolytic process Source: RefGenome
  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 – 465465Glucokinase
PRO_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.

Family & Domainsi

Domains and Repeats

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

Region

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

Sequence similaritiesi

Belongs to the hexokinase family.

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

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 1515MLDDR…TKKEK → MAVDTTRRGAQSLTL in isoform 2.
VSP_002076Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti133 – 1331F → L in AAA37703. 1 Publication
Sequence conflicti159 – 1591I → L in AAA37703. 1 Publication

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

« 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: September 3, 2014
This is version 120 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

Similar proteinsi