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P17712

- HXK4_RAT

UniProt

P17712 - HXK4_RAT

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Protein

Glucokinase

Gene
Gck
Organism
Rattus norvegicus (Rat)
Status
Reviewed - 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.

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.1 Publication

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: RGD
  2. ATP binding Source: UniProtKB
  3. glucokinase activity Source: UniProtKB
  4. glucose binding Source: UniProtKB
  5. magnesium ion binding Source: RGD
  6. protein binding Source: BHF-UCL
  7. protein phosphatase binding Source: RGD

GO - Biological processi

  1. calcium ion import Source: Ensembl
  2. carbohydrate phosphorylation Source: RGD
  3. cellular glucose homeostasis Source: RGD
  4. cellular response to glucose starvation Source: RGD
  5. cellular response to insulin stimulus Source: BHF-UCL
  6. cellular response to leptin stimulus Source: BHF-UCL
  7. detection of glucose Source: UniProtKB
  8. fructose 2,6-bisphosphate metabolic process Source: RGD
  9. glucose 6-phosphate metabolic process Source: RGD
  10. glucose homeostasis Source: UniProtKB
  11. glucose metabolic process Source: RGD
  12. glycogen biosynthetic process Source: RGD
  13. glycolytic process Source: RGD
  14. lipid homeostasis Source: RGD
  15. NADP metabolic process Source: Ensembl
  16. negative regulation of epinephrine secretion Source: RGD
  17. negative regulation of gluconeogenesis Source: UniProtKB
  18. positive regulation of cytosolic calcium ion concentration Source: RGD
  19. positive regulation of glycogen biosynthetic process Source: UniProtKB
  20. positive regulation of glycolytic process Source: RGD
  21. positive regulation of insulin secretion Source: UniProtKB
  22. positive regulation of phosphorylation Source: RGD
  23. regulation of potassium ion transport Source: Ensembl
  24. response to glucose Source: RGD
  25. second-messenger-mediated signaling Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase

Keywords - Biological processi

Glycolysis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiREACT_205960. Glucose transport.
SABIO-RKP17712.

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Chromosome 14

Organism-specific databases

RGDi2670. Gck.

Subcellular locationi

Cytoplasm. Nucleus
Note: Under low glucose concentrations, GCK associates with GKRP and the inactive complex is recruited to the hepatocyte nucleus.1 Publication

GO - Cellular componenti

  1. basal cortex Source: RGD
  2. cell cortex Source: RGD
  3. cytoplasm Source: BHF-UCL
  4. cytosol Source: RGD
  5. mitochondrion Source: RGD
  6. nucleoplasm Source: RGD
  7. nucleus Source: BHF-UCL
  8. secretory granule Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 465465GlucokinasePRO_0000197595Add
BLAST

Proteomic databases

PRIDEiP17712.

Expressioni

Tissue specificityi

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

Gene expression databases

GenevestigatoriP17712.

Interactioni

Subunit structurei

Monomer By similarity.

Protein-protein interaction databases

IntActiP17712. 2 interactions.
MINTiMINT-1795103.

Structurei

3D structure databases

ProteinModelPortaliP17712.
SMRiP17712. Positions 16-461.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini12 – 217206Hexokinase type-1Add
BLAST
Domaini219 – 458240Hexokinase type-2Add
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.
GeneTreeiENSGT00390000017159.
HOGENOMiHOG000162670.
HOVERGENiHBG000142.
KOiK12407.
OMAiRCEITFL.
OrthoDBiEOG7S21X5.
PhylomeDBiP17712.

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 (3)i

Sequence statusi: Complete.

This entry describes 3 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: 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

MLDDRARMEA TKKEKVEQIL AEFQLQEEDL KKVMSRMQKE MDRGLRLETH    50
EEASVKMLPT YVRSTPEGSE VGDFLSLDLG GTNFRVMLVK VGEGEAGQWS 100
VKTKHQMYSI PEDAMTGTAE MLFDYISECI SDFLDKHQMK HKKLPLGFTF 150
SFPVRHEDLD KGILLNWTKG FKASGAEGNN IVGLLRDAIK RRGDFEMDVV 200
AMVNDTVATM ISCYYEDRQC EVGMIVGTGC NACYMEEMQN VELVEGDEGR 250
MCVNTEWGAF GDSGELDEFL LEYDRMVDES SANPGQQLYE KIIGGKYMGE 300
LVRLVLLKLV DENLLFHGEA SEQLRTRGAF ETRFVSQVES DSGDRKQIHN 350
ILSTLGLRPS VTDCDIVRRA CESVSTRAAH MCSAGLAGVI NRMRESRSED 400
VMRITVGVDG SVYKLHPSFK ERFHASVRRL TPNCEITFIE SEEGSGRGAA 450
LVSAVACKKA CMLAQ 465
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)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 1515MLDDR…TKKEK → MAMDTTRCGAQLLTL in isoform 3. VSP_002077Add
BLAST
Alternative sequencei122 – 13817Missing in isoform 2. VSP_002078Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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_006251179.1. [P17712-1]
UniGeneiRn.10447.

Genome annotation databases

EnsembliENSRNOT00000019625; ENSRNOP00000019625; ENSRNOG00000014447. [P17712-3]
GeneIDi24385.
KEGGirno:24385.
UCSCiRGD:2670. rat. [P17712-1]

Keywords - Coding sequence diversityi

Alternative promoter usage, Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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 .
PIRi A31810.
I84740.
RefSeqi NP_001257779.1. NM_001270850.1. [P17712-2 ]
NP_036697.1. NM_012565.2. [P17712-3 ]
XP_006251241.1. XM_006251179.1. [P17712-1 ]
UniGenei Rn.10447.

3D structure databases

ProteinModelPortali P17712.
SMRi P17712. Positions 16-461.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi P17712. 2 interactions.
MINTi MINT-1795103.

Chemistry

BindingDBi P17712.
ChEMBLi CHEMBL3882.

Proteomic databases

PRIDEi P17712.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSRNOT00000019625 ; ENSRNOP00000019625 ; ENSRNOG00000014447 . [P17712-3 ]
GeneIDi 24385.
KEGGi rno:24385.
UCSCi RGD:2670. rat. [P17712-1 ]

Organism-specific databases

CTDi 2645.
RGDi 2670. Gck.

Phylogenomic databases

eggNOGi COG5026.
GeneTreei ENSGT00390000017159.
HOGENOMi HOG000162670.
HOVERGENi HBG000142.
KOi K12407.
OMAi RCEITFL.
OrthoDBi EOG7S21X5.
PhylomeDBi P17712.

Enzyme and pathway databases

Reactomei REACT_205960. Glucose transport.
SABIO-RK P17712.

Miscellaneous databases

NextBioi 603157.

Gene expression databases

Genevestigatori P17712.

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

  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. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-15 (ISOFORM 3).
  5. 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).
  7. "Glucokinase regulatory protein is essential for the proper subcellular localisation of liver glucokinase."
    de la Iglesia N., Veiga-da-Cunha M., Van Schaftingen E., Guinovart J.J., Ferrer J.C.
    FEBS Lett. 456:332-338(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: ENZYME REGULATION, SUBCELLULAR LOCATION.

Entry informationi

Entry nameiHXK4_RAT
AccessioniPrimary (citable) accession number: P17712
Secondary accession number(s): P17711
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: November 1, 1990
Last modified: September 3, 2014
This is version 122 of the entry and version 2 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, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi