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Reviewed, UniProtKB/Swiss-Prot P17712 (HXK4_RAT)

Last modified October 13, 2009. Version 88. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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)
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length465 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
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.

Ontologies

Keywords
   Biological processGlycolysis
   Coding sequence diversityAlternative promoter usage
Alternative splicing
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Transferase
   Technical termDirect protein sequencing
Gene Ontology (GO)
   Biological processcarbohydrate phosphorylation

Inferred from direct assay. Source: RGD

cellular glucose homeostasis

Inferred from mutant phenotype. Source: RGD

cellular response to glucose starvation

Inferred from mutant phenotype. Source: RGD

detection of glucose

Inferred from sequence or structural similarity. Source: UniProtKB

elevation of cytosolic calcium ion concentration

Inferred from direct assay. Source: RGD

fructose 2,6-bisphosphate metabolic process

Inferred from direct assay. Source: RGD

glucose 6-phosphate metabolic process

Inferred from direct assay. Source: RGD

glycogen biosynthetic process

Inferred from direct assay. Source: RGD

glycolysis

Inferred from direct assay. Source: RGD

negative regulation of epinephrine secretion

Inferred from mutant phenotype. Source: RGD

negative regulation of gluconeogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of glycogen biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of glycolysis

Inferred from direct assay. Source: RGD

positive regulation of insulin secretion

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of phosphorylation

Inferred from direct assay. Source: RGD

second-messenger-mediated signaling

Inferred from direct assay. Source: RGD

   Cellular componentcell cortex part

Inferred from direct assay. Source: RGD

cytosol

Inferred from direct assay. Source: RGD

mitochondrion

Inferred from direct assay. Source: RGD

nucleoplasm

Inferred from direct assay. Source: RGD

secretory granule

Inferred from direct assay. Source: RGD

   Molecular functionADP binding

Inferred from direct assay. 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. Source: RGD

protein phosphatase binding

Inferred from physical interaction. 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

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.

Checksum: 4925A5DD0CA2668B
Show »

FASTA44850,061
Isoform 3.

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: 2909525] [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: 2396986] [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: 2550428] [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: 2662183] [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: 2590200] [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: 1999433] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-166 (ISOFORM 1).
+Additional computationally mapped references.

Cross-references

Sequence databases

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.
IPIIPI00190888.
IPI00202358.
IPI00231947.
PIRA31810.
I84740.
RefSeqNP_036697.1.
UniGeneRn.10447

3D structure databases

HSSPHSSP built from PDB template 1QHA based on UniProtKB P19367.
SMRP17712. Positions 16-461.
ModBaseSearch...

Protein-protein interaction databases

STRINGP17712.

Genome annotation databases

EnsemblENSRNOT00000019625; ENSRNOP00000019625; ENSRNOG00000014447; Rattus norvegicus. [Genome view]
ENSRNOT00000043053; ENSRNOP00000043229; ENSRNOG00000014447; Rattus norvegicus. [Genome view]
GeneID24385.
KEGGrno:24385.
UCSCM25807. rat.

Organism-specific databases

CTD24385.
RGD2670. Gck.

Phylogenomic databases

HOVERGENP17712.

Enzyme and pathway databases

BRENDA2.7.1.2. 248.

Gene expression databases

ArrayExpressP17712.
GenevestigatorP17712.
GermOnlineENSRNOG00000014447. Rattus norvegicus.

Family and domain databases

InterProIPR001312. Hexokinase.
IPR019807. Hexokinase_CS.
[Graphical view]
PANTHERPTHR19443. Hexokinase. 1 hit.
PfamPF00349. Hexokinase_1. 1 hit.
PF03727. Hexokinase_2. 1 hit.
[Graphical view]
PRINTSPR00475. HEXOKINASE.
ProDomPD001109. Hexokinase. 1 hit.
[Graphical view] [Entries sharing at least one domain]
PROSITEPS00378. HEXOKINASES. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

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: October 13, 2009
This is version 88 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents