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P17712 (HXK4_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 119. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | 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
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length465 AA.
Sequence statusComplete.
Protein existenceEvidence at protein 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.

Subunit structure

Monomer By similarity.

Tissue specificity

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

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
   Coding sequence diversityAlternative promoter usage
Alternative splicing
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Transferase
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processNADP metabolic process

Inferred from electronic annotation. Source: Ensembl

calcium ion import

Inferred from electronic annotation. Source: Ensembl

carbohydrate phosphorylation

Inferred from direct assay PubMed 15138155PubMed 9109397. Source: RGD

cellular glucose homeostasis

Inferred from mutant phenotype PubMed 16443775. Source: RGD

cellular response to glucose starvation

Inferred from mutant phenotype PubMed 18292346. Source: RGD

cellular response to insulin stimulus

Inferred from direct assay PubMed 17470517. Source: BHF-UCL

cellular response to leptin stimulus

Inferred from direct assay PubMed 17470517. Source: BHF-UCL

detection of glucose

Inferred from sequence or structural similarity. Source: UniProtKB

fructose 2,6-bisphosphate metabolic process

Inferred from direct assay PubMed 17553851. Source: RGD

glucose 6-phosphate metabolic process

Inferred from direct assay PubMed 15138155PubMed 4273555. Source: RGD

glucose homeostasis

Inferred from sequence or structural similarity. Source: UniProtKB

glucose metabolic process

Inferred from direct assay PubMed 17553851. Source: RGD

glycogen biosynthetic process

Inferred from direct assay PubMed 17028192. Source: RGD

glycolysis

Inferred from direct assay PubMed 4273555PubMed 4353083. Source: RGD

lipid homeostasis

Inferred from direct assay PubMed 22925001. Source: RGD

negative regulation of epinephrine secretion

Inferred from mutant phenotype PubMed 18292346. Source: RGD

negative regulation of gluconeogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cytosolic calcium ion concentration

Inferred from direct assay PubMed 17360975. Source: RGD

positive regulation of glycogen biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of glycolysis

Inferred from direct assay PubMed 17553851. Source: RGD

positive regulation of insulin secretion

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of phosphorylation

Inferred from direct assay PubMed 17553851. Source: RGD

regulation of potassium ion transport

Inferred from electronic annotation. Source: Ensembl

response to glucose

Inferred from expression pattern PubMed 12086933. Source: RGD

second-messenger-mediated signaling

Inferred from direct assay PubMed 11250924. Source: RGD

   Cellular_componentbasal cortex

Inferred from direct assay PubMed 10071239. Source: RGD

cell cortex

Inferred from direct assay PubMed 12369705. Source: RGD

cytoplasm

Inferred from direct assay PubMed 10601273. Source: BHF-UCL

cytosol

Inferred from direct assay PubMed 16542652. Source: RGD

mitochondrion

Inferred from direct assay PubMed 16542652. Source: RGD

nucleoplasm

Inferred from direct assay PubMed 12369705. Source: RGD

nucleus

Inferred from direct assay PubMed 10601273. Source: BHF-UCL

secretory granule

Inferred from direct assay PubMed 10461810PubMed 9357983. Source: RGD

   Molecular_functionADP binding

Inferred from direct assay PubMed 12513690. Source: RGD

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 direct assay PubMed 12513690. Source: RGD

protein phosphatase binding

Inferred from physical interaction PubMed 10913113. Source: RGD

Complete GO annotation...

Alternative products

This entry describes 3 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: P17712-1)

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: P17712-2)

The sequence of this isoform differs from the canonical sequence as follows:
     122-138: Missing.
Isoform 3 (identifier: P17712-3)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 465465Glucokinase
PRO_0000197595

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 → MAMDTTRCGAQLLTL in isoform 3.
VSP_002077
Alternative sequence122 – 13817Missing in isoform 2.
VSP_002078

Sequences

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

Last modified November 1, 1990. Version 2.
Checksum: 65B36673DF9297BE

FASTA46552,116
        10         20         30         40         50         60 
MLDDRARMEA TKKEKVEQIL AEFQLQEEDL KKVMSRMQKE MDRGLRLETH EEASVKMLPT 

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

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

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

       250        260        270        280        290        300 
VELVEGDEGR MCVNTEWGAF GDSGELDEFL LEYDRMVDES SANPGQQLYE KIIGGKYMGE 

       310        320        330        340        350        360 
LVRLVLLKLV DENLLFHGEA SEQLRTRGAF ETRFVSQVES DSGDRKQIHN ILSTLGLRPS 

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

       430        440        450        460 
ERFHASVRRL TPNCEITFIE SEEGSGRGAA LVSAVACKKA CMLAQ 

« Hide

Isoform 2 [UniParc].

Checksum: 4925A5DD0CA2668B
Show »

FASTA44850,061
Isoform 3 [UniParc].

Checksum: 7495EE087FE4F8C7
Show »

FASTA46551,919

References

[1]"The amino acid sequence of rat liver glucokinase deduced from cloned cDNA."
Andreone T.L., Printz R.L., Pilkis S.J., Magnuson M.A., Granner D.K.
J. Biol. Chem. 264:363-369(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), PARTIAL PROTEIN SEQUENCE.
Tissue: Liver.
[2]"Alternative splicing of glucokinase mRNA in rat liver."
Hayzer D.J., Iynedjian P.B.
Biochem. J. 270:261-263(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], ALTERNATIVE SPLICING.
Tissue: Liver.
[3]"An alternate promoter in the glucokinase gene is active in the pancreatic beta cell."
Magnuson M.A., Shelton K.D.
J. Biol. Chem. 264:15936-15942(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 1-15 (ISOFORM 1).
Tissue: Pancreas.
[4]"Rat glucokinase gene: structure and regulation by insulin."
Magnuson M.A., Andeone T.L., Printz R.L., Koch S., Granner D.K.
Proc. Natl. Acad. Sci. U.S.A. 86:4838-4842(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-15 (ISOFORM 3).
[5]"Characterization of the 5' flanking region of rat glucokinase gene."
Noguchi T., Takenaka M., Yamada K., Matsuda T., Hashimoto M., Tanaka T.
Biochem. Biophys. Res. Commun. 164:1247-1252(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE OF 1-15 (ISOFORM 3).
[6]"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).
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J04218 mRNA. Translation: AAA41229.1.
M24952 expand/collapse EMBL AC list , 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.
PIRA31810.
I84740.
RefSeqNP_001257779.1. NM_001270850.1.
NP_036697.1. NM_012565.2.
XP_006251241.1. XM_006251179.1.
UniGeneRn.10447.

3D structure databases

ProteinModelPortalP17712.
SMRP17712. Positions 16-461.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP17712. 2 interactions.
MINTMINT-1795103.

Chemistry

BindingDBP17712.
ChEMBLCHEMBL3882.

Proteomic databases

PRIDEP17712.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000019625; ENSRNOP00000019625; ENSRNOG00000014447. [P17712-3]
GeneID24385.
KEGGrno:24385.
UCSCRGD:2670. rat. [P17712-1]

Organism-specific databases

CTD2645.
RGD2670. Gck.

Phylogenomic databases

eggNOGCOG5026.
GeneTreeENSGT00390000017159.
HOGENOMHOG000162670.
HOVERGENHBG000142.
KOK12407.
OMADESSANP.
OrthoDBEOG7S21X5.
PhylomeDBP17712.

Enzyme and pathway databases

SABIO-RKP17712.

Gene expression databases

GenevestigatorP17712.

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

NextBio603157.

Entry information

Entry nameHXK4_RAT
AccessionPrimary (citable) accession number: P17712
Secondary accession number(s): P17711
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: November 1, 1990
Last modified: April 16, 2014
This is version 119 of the entry and version 2 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