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P52792 (HXK4_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 119. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Gck
Synonyms:Gk
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length465 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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 activity

ATP + D-glucose = ADP + D-glucose 6-phosphate.

Enzyme regulation

Low glucose and high fructose-6-phosphate triggers association with the inhibitor GKRP followed by sequestration in the nucleus By similarity.

Subunit structure

Monomer By similarity.

Subcellular location

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.

Tissue specificity

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

Miscellaneous

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

Sequence similarities

Belongs to the hexokinase family.

Contains 1 hexokinase type-1 domain.

Contains 1 hexokinase type-2 domain.

Ontologies

Keywords
   Biological processGlycolysis
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative promoter usage
Alternative splicing
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Transferase
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processNADP metabolic process

Inferred from mutant phenotype PubMed 9873043. Source: MGI

calcium ion import

Inferred from mutant phenotype PubMed 18477811. Source: UniProtKB

carbohydrate phosphorylation

Inferred from direct assay PubMed 141272PubMed 3931624. Source: MGI

cellular glucose homeostasis

Inferred from mutant phenotype PubMed 7553875. Source: MGI

cellular response to glucose starvation

Inferred from electronic annotation. Source: Ensembl

cellular response to insulin stimulus

Inferred from electronic annotation. Source: Ensembl

cellular response to leptin stimulus

Inferred from electronic annotation. Source: Ensembl

detection of glucose

Inferred from sequence or structural similarity. Source: UniProtKB

endocrine pancreas development

Traceable author statement. Source: Reactome

fructose 2,6-bisphosphate metabolic process

Inferred from electronic annotation. Source: Ensembl

glucose homeostasis

Inferred from mutant phenotype PubMed 18477811. Source: UniProtKB

glucose metabolic process

Inferred from direct assay PubMed 141272PubMed 3931624. Source: MGI

glycogen biosynthetic process

Inferred from electronic annotation. Source: Ensembl

glycolytic process

Inferred from Biological aspect of Ancestor. Source: RefGenome

negative regulation of epinephrine secretion

Inferred from electronic annotation. Source: Ensembl

negative regulation of gluconeogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cytosolic calcium ion concentration

Inferred from electronic annotation. Source: Ensembl

positive regulation of glycogen biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of glycolytic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of insulin secretion

Inferred from mutant phenotype PubMed 18477811. Source: UniProtKB

positive regulation of phosphorylation

Inferred from electronic annotation. Source: Ensembl

regulation of insulin secretion

Inferred from mutant phenotype PubMed 8530440PubMed 8954920. Source: MGI

regulation of potassium ion transport

Inferred from mutant phenotype PubMed 9662046. Source: MGI

second-messenger-mediated signaling

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcell cortex

Inferred from electronic annotation. Source: Ensembl

cytosol

Inferred from direct assay PubMed 24187134. Source: MGI

mitochondrion

Inferred from direct assay PubMed 12931191PubMed 14651853. Source: MGI

nucleoplasm

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from direct assay PubMed 10713097. Source: BHF-UCL

secretory granule

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionADP binding

Inferred from electronic annotation. Source: Ensembl

ATP binding

Inferred from sequence or structural similarity. Source: UniProtKB

glucokinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

glucose binding

Inferred from sequence or structural similarity. Source: UniProtKB

magnesium ion binding

Inferred from electronic annotation. Source: Ensembl

protein binding

Inferred from physical interaction PubMed 18223655. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative promoter usage and alternative splicing. [Align] [Select]

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)

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.
Isoform 2 (identifier: P52792-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 465465Glucokinase
PRO_0000197594

Regions

Domain12 – 217206Hexokinase type-1
Domain219 – 458240Hexokinase type-2
Nucleotide binding78 – 836ATP Potential
Nucleotide binding295 – 2962ATP By similarity
Nucleotide binding332 – 3365ATP By similarity
Nucleotide binding411 – 4155ATP By similarity
Region151 – 1522Substrate binding By similarity
Region168 – 1692Substrate binding By similarity
Region204 – 2052Substrate binding By similarity

Sites

Binding site1041ATP Potential
Binding site2281ATP By similarity
Binding site2311Substrate By similarity
Binding site2561Substrate By similarity
Binding site2901Substrate By similarity

Natural variations

Alternative sequence1 – 1515MLDDR…TKKEK → MAVDTTRRGAQSLTL in isoform 2.
VSP_002076

Experimental info

Sequence conflict1331F → L in AAA37703. Ref.4
Sequence conflict1591I → L in AAA37703. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: 8C85EED079A52D61

FASTA46552,089
        10         20         30         40         50         60 
MLDDRARMEA TKKEKVEQIL AEFQLQEEDL KKVMSRMQKE MDRGLKLETH QEASVKMLPT 

        70         80         90        100        110        120 
YVRSTPEGSE VGDFLSLDLG GTNFRVMLVK VGEGEAGQWS VKTKHQMYSI PEDAMTGTAE 

       130        140        150        160        170        180 
MLFDYISECI SDFLDKHQMK HKKLPLGFTF SFPVRHEDID KGILLNWTKG FKASGAEGNN 

       190        200        210        220        230        240 
IVGLLRDAIK RRGDFEMDVV AMVNDTVATM ISCYYEDRQC EVGMIVGTGC NACYMEEMQN 

       250        260        270        280        290        300 
VELVEGDEGR MCVNTEWGAF GNSGELDEFL LEYDRMVDES SVNPGQQLYE KIIGGKYMGE 

       310        320        330        340        350        360 
LVRLVLLKLV EENLLFHGEA SEQLRTRGAF ETRFVSQVES DSGDRRQILN ILSTLGLRPS 

       370        380        390        400        410        420 
VADCDIVRRA CESVSTRAAH MCSAGLAGVI NRMRESRSED VMRITVGVDG SVYKLHPSFK 

       430        440        450        460 
ERFHASVRRL TPNCEITFIE SEEGSGRGAA LVSAVACKKA CMLGQ 

« Hide

Isoform 2 [UniParc].

Checksum: DAC911920818B811
Show »

FASTA46551,886

References

« Hide 'large scale' references
[1]"Partial structure of the mouse glucokinase gene."
Ishimura-Oka K., Nakamuta M., Chu M.J., Sullivan M., Chan L., Oka K.
Genomics 29:751-754(1995) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L38990 mRNA. Translation: AAB00360.1.
L41631 Genomic DNA. Translation: AAC42074.1.
BC011139 mRNA. Translation: AAH11139.1.
M58755 mRNA. Translation: AAA37703.1.
CCDSCCDS24409.1. [P52792-1]
CCDS70135.1. [P52792-2]
PIRI49693.
I49694.
RefSeqNP_001274315.1. NM_001287386.1. [P52792-2]
NP_034422.2. NM_010292.5. [P52792-1]
UniGeneMm.220358.

3D structure databases

ProteinModelPortalP52792.
SMRP52792. Positions 16-460.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid222262. 3 interactions.

PTM databases

PhosphoSiteP52792.

Proteomic databases

MaxQBP52792.
PaxDbP52792.
PRIDEP52792.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000102920; ENSMUSP00000099984; ENSMUSG00000041798. [P52792-1]
ENSMUST00000109822; ENSMUSP00000105447; ENSMUSG00000041798. [P52792-2]
ENSMUST00000109823; ENSMUSP00000105448; ENSMUSG00000041798. [P52792-2]
GeneID103988.
KEGGmmu:103988.
UCSCuc007hxn.1. mouse. [P52792-1]

Organism-specific databases

CTD2645.
MGIMGI:1270854. Gck.

Phylogenomic databases

eggNOGCOG5026.
HOGENOMHOG000162670.
HOVERGENHBG000142.
KOK12407.
OMARCEITFL.
OrthoDBEOG7S21X5.
PhylomeDBP52792.
TreeFamTF314238.

Enzyme and pathway databases

ReactomeREACT_13641. Regulation of Beta-Cell Development.
REACT_188576. Developmental Biology.
SABIO-RKP52792.

Gene expression databases

ArrayExpressP52792.
BgeeP52792.
CleanExMM_GCK.
GenevestigatorP52792.

Family and domain databases

InterProIPR001312. Hexokinase.
IPR022673. Hexokinase_C.
IPR019807. Hexokinase_CS.
IPR022672. Hexokinase_N.
[Graphical view]
PANTHERPTHR19443. PTHR19443. 1 hit.
PfamPF00349. Hexokinase_1. 1 hit.
PF03727. Hexokinase_2. 1 hit.
[Graphical view]
PRINTSPR00475. HEXOKINASE.
PROSITEPS00378. HEXOKINASES. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio356305.
PROP52792.
SOURCESearch...

Entry information

Entry nameHXK4_MOUSE
AccessionPrimary (citable) accession number: P52792
Secondary accession number(s): P52791
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: July 9, 2014
This is version 119 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot