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P35557 (HXK4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 159. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

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. Glucokinase has a high Km for glucose, and so it is effective only when glucose is abundant. The role of GCK is to provide G6P for the synthesis of glycogen. 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

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. Subject to allosteric regulation. Low glucose and high fructose-6-phosphate triggers association with the inhibitor GKRP followed by sequestration in the nucleus. Ref.12 Ref.14

Subunit structure

Monomer. Ref.14

Subcellular location

Cytoplasm. Nucleus. Note: Under low glucose concentrations, GCK associates with GKRP and the inactive complex is recruited to the hepatocyte nucleus. Ref.12

Tissue specificity

Isoform 1 is expressed in pancreas. Isoform 2 and isoform 3 is expressed in liver.

Involvement in disease

Maturity-onset diabetes of the young 2 (MODY2) [MIM:125851]: A form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5 Ref.7 Ref.17 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.27 Ref.28 Ref.29

Familial hyperinsulinemic hypoglycemia 3 (HHF3) [MIM:602485]: Most common cause of persistent hypoglycemia in infancy. Unless early and aggressive intervention is undertaken, brain damage from recurrent episodes of hypoglycemia may occur.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.26

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 splicing
Polymorphism
   DiseaseDiabetes mellitus
Disease mutation
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Transferase
   Technical term3D-structure
Allosteric enzyme
Complete proteome
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 metabolic process

Traceable author statement. Source: Reactome

cellular glucose homeostasis

Inferred from Biological aspect of Ancestor. Source: RefGenome

cellular response to glucose starvation

Inferred from electronic annotation. Source: Ensembl

cellular response to insulin stimulus

Inferred from sequence or structural similarity. Source: BHF-UCL

cellular response to leptin stimulus

Inferred from sequence or structural similarity. Source: BHF-UCL

detection of glucose

Inferred from mutant phenotype PubMed 12941786. 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 8132752. Source: UniProtKB

glucose metabolic process

Inferred from electronic annotation. Source: Ensembl

glucose transport

Traceable author statement. Source: Reactome

glycogen biosynthetic process

Inferred from electronic annotation. Source: Ensembl

glycolytic process

Inferred from electronic annotation. Source: UniProtKB-KW

hexose transport

Traceable author statement. Source: Reactome

negative regulation of epinephrine secretion

Inferred from electronic annotation. Source: Ensembl

negative regulation of gluconeogenesis

Inferred from mutant phenotype PubMed 8878425. Source: UniProtKB

positive regulation of cytosolic calcium ion concentration

Inferred from electronic annotation. Source: Ensembl

positive regulation of glycogen biosynthetic process

Inferred from mutant phenotype PubMed 8878425. Source: UniProtKB

positive regulation of glycolytic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of insulin secretion

Inferred from mutant phenotype PubMed 8132752PubMed 8878425. Source: UniProtKB

positive regulation of phosphorylation

Inferred from electronic annotation. Source: Ensembl

regulation of glucose transport

Traceable author statement. Source: Reactome

regulation of glycolytic process

Non-traceable author statement PubMed 9570959. Source: BHF-UCL

regulation of insulin secretion

Inferred from mutant phenotype PubMed 20668700. Source: BHF-UCL

regulation of potassium ion transport

Inferred from electronic annotation. Source: Ensembl

second-messenger-mediated signaling

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

transmembrane transport

Traceable author statement. Source: Reactome

   Cellular_componentcell cortex

Inferred from electronic annotation. Source: Ensembl

cytosol

Traceable author statement. Source: Reactome

mitochondrion

Inferred from electronic annotation. Source: Ensembl

nucleoplasm

Traceable author statement. Source: Reactome

secretory granule

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionADP binding

Inferred from electronic annotation. Source: Ensembl

ATP binding

Inferred from direct assay PubMed 12941786PubMed 16173921Ref.21. Source: UniProtKB

glucokinase activity

Inferred from direct assay PubMed 12941786PubMed 16173921Ref.21. Source: UniProtKB

glucose binding

Inferred from direct assay PubMed 12941786PubMed 16173921Ref.21. Source: UniProtKB

magnesium ion binding

Inferred from electronic annotation. Source: Ensembl

protein binding

Inferred from physical interaction PubMed 16173921. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

GCKRQ143972EBI-709928,EBI-709948
PFKFB1P161182EBI-709928,EBI-709807

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P35557-1)

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: P35557-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-15: MLDDRARMEAAKKEK → MAMDVTRSQAQTALTL
Isoform 3 (identifier: P35557-3)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 465465Glucokinase
PRO_0000197593

Regions

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

Sites

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

Natural variations

Alternative sequence1 – 1515MLDDR…AKKEK → MAMDVTRSQAQTALTL in isoform 2.
VSP_002074
Alternative sequence1 – 1515MLDDR…AKKEK → MPRPRSQLPQPNSQ in isoform 3.
VSP_002075
Natural variant41D → N. Ref.20
VAR_003692
Natural variant111A → T. Ref.18
Corresponds to variant rs116093166 [ dbSNP | Ensembl ].
VAR_010583
Natural variant361R → W in MODY2. Ref.22
VAR_010584
Natural variant531A → S in MODY2.
VAR_010585
Natural variant701E → K in MODY2; large increase in Km for glucose. Ref.20
VAR_003693
Natural variant801G → A in MODY2.
VAR_003694
Natural variant801G → S in MODY2. Ref.24
VAR_003695
Natural variant1071M → T. Ref.2 Ref.7
VAR_003696
Natural variant1081Y → H in MODY2. Ref.25
VAR_010586
Natural variant1101I → T in MODY2. Ref.27
VAR_012352
Natural variant1191A → D in MODY2. Ref.27
VAR_012353
Natural variant1311S → P in MODY2; significant increase in the Km and in the affinity for ATP. Ref.19 Ref.20
VAR_003697
Natural variant1371H → R in MODY2.
VAR_010587
Natural variant1501F → S in MODY2. Ref.25
VAR_010588
Natural variant1641L → P in MODY2. Ref.28
VAR_012350
Natural variant1681T → P in MODY2.
VAR_010589
Natural variant1751G → R in MODY2.
VAR_003698
Natural variant1821V → M in MODY2.
VAR_003699
Natural variant1881A → T in MODY2; large increase in Km for glucose. Ref.20
VAR_003700
Natural variant2031V → A in MODY2.
VAR_003701
Natural variant2091T → M in MODY2. Ref.22
VAR_010590
Natural variant2101M → K in MODY2. Ref.29
VAR_012351
Natural variant2101M → T in MODY2.
VAR_010591
Natural variant2131C → R in MODY2.
VAR_010592
Natural variant2211E → K in MODY2. Ref.24
VAR_003702
Natural variant2261V → M in MODY2.
VAR_003703
Natural variant2271G → C in MODY2. Ref.24
VAR_003704
Natural variant2281T → M in MODY2. Ref.5 Ref.29
VAR_003705
Natural variant2561E → K in MODY2.
VAR_003706
Natural variant2571W → R in MODY2; almost complete loss of activity. Ref.20
VAR_003707
Natural variant2591A → T in MODY2. Ref.25
VAR_010593
Natural variant2611G → E in MODY2. Ref.22
VAR_010594
Natural variant2611G → R in MODY2. Ref.5 Ref.7
VAR_003708
Natural variant2791E → Q in MODY2.
Corresponds to variant rs104894005 [ dbSNP | Ensembl ].
VAR_003709
Natural variant2991G → R in MODY2. Ref.17 Ref.25
VAR_003710
Natural variant3001E → K in MODY2.
VAR_003712
Natural variant3001E → Q in MODY2.
VAR_003711
Natural variant3091L → P in MODY2.
VAR_003713
Natural variant3361S → L in MODY2.
VAR_010595
Natural variant3421T → P. Ref.30
VAR_066615
Natural variant3671V → M in MODY2.
VAR_010596
Natural variant3821C → Y in MODY2. Ref.25
VAR_010597
Natural variant3841A → T in MODY2. Ref.25
VAR_010598
Natural variant3851G → V in MODY2. Ref.27
VAR_012354
Natural variant3921R → C in MODY2. Ref.25
VAR_010599
Natural variant4141K → E in MODY2; large increase in Km for glucose. Ref.20
VAR_003714
Natural variant4551V → M in HHF3. Ref.26
VAR_003715

Experimental info

Mutagenesis1771E → K: Small change in activity.
Mutagenesis2561E → A: Inactive enzyme.
Mutagenesis4141K → A: Small change in activity.

Secondary structure

.......................................................................... 465
Helix Strand Turn

Details...

Sequences

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

Last modified June 1, 1994. Version 1.
Checksum: 094D4A2F78096724

FASTA46552,191
        10         20         30         40         50         60 
MLDDRARMEA AKKEKVEQIL AEFQLQEEDL KKVMRRMQKE MDRGLRLETH EEASVKMLPT 

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

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

       190        200        210        220        230        240 
VVGLLRDAIK RRGDFEMDVV AMVNDTVATM ISCYYEDHQC EVGMIVGTGC NACYMEEMQN 

       250        260        270        280        290        300 
VELVEGDEGR MCVNTEWGAF GDSGELDEFL LEYDRLVDES SANPGQQLYE KLIGGKYMGE 

       310        320        330        340        350        360 
LVRLVLLRLV DENLLFHGEA SEQLRTRGAF ETRFVSQVES DTGDRKQIYN ILSTLGLRPS 

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

       430        440        450        460 
ERFHASVRRL TPSCEITFIE SEEGSGRGAA LVSAVACKKA CMLGQ 

« Hide

Isoform 2 [UniParc].

Checksum: A44B768452105627
Show »

FASTA46652,136
Isoform 3 [UniParc].

Checksum: 5FA1020BBF98A4E9
Show »

FASTA46452,035

References

« Hide 'large scale' references
[1]"Human glucokinase gene: isolation, structural characterization, and identification of a microsatellite repeat polymorphism."
Tanizawa Y., Matsutani A., Chiu K.C., Permutt M.A.
Mol. Endocrinol. 6:1070-1081(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"Human liver glucokinase gene: cloning and sequence determination of two alternatively spliced cDNAs."
Tanizawa Y., Koranyi L.I., Welling C.M., Permutt M.A.
Proc. Natl. Acad. Sci. U.S.A. 88:7294-7297(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT THR-107.
[3]"Human pancreatic beta-cell glucokinase: cDNA sequence and localization of the polymorphic gene to chromosome 7, band p13."
Nishi S., Stoffel M., Xiang K.S., Shows T.B., Bell G.I., Takeda J.
Diabetologia 35:743-747(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Pancreas.
[4]"Human islet glucokinase gene. Isolation and sequence analysis of full-length cDNA."
Koranyi L.I., Tanizawa Y., Welling C.M., Rabin D.U., Permutt M.A.
Diabetes 41:807-811(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Pancreas.
[5]"Human glucokinase gene: isolation, characterization, and identification of two missense mutations linked to early-onset non-insulin-dependent (type 2) diabetes mellitus."
Stoffel M., Froguel P., Takeda J., Zouali H., Vionnet N., Nishi S., Weber I.T., Harrison R.W., Pilkis S.J., Lesage S., Vaxillaire M., Velho G., Sun F., Iris F., Passa P., Cohen D., Bell G.I.
Proc. Natl. Acad. Sci. U.S.A. 89:7698-7702(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS MODY2 MET-228 AND ARG-261.
Tissue: Placenta.
[6]Erratum
Stoffel M., Froguel P., Takeda J., Zouali H., Vionnet N., Nishi S., Weber I.T., Harrison R.W., Pilkis S.J., Lesage S., Vaxillaire M., Velho G., Sun F., Iris F., Passa P., Cohen D., Bell G.I.
Proc. Natl. Acad. Sci. U.S.A. 89:10562-10562(1992)
[7]"Structure of the human glucokinase gene and identification of a missense mutation in a Japanese patient with early-onset non-insulin-dependent diabetes mellitus."
Sakura H., Eto K., Kadowaki H., Simokawa K., Ueno H., Koda N., Fukushima Y., Akanuma Y., Yazaki Y., Kadowaki T.
J. Clin. Endocrinol. Metab. 75:1571-1573(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT THR-107, VARIANT MODY2 ARG-261.
[8]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Liver.
[9]"Human chromosome 7: DNA sequence and biology."
Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. expand/collapse author list , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C.
Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[11]"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].
Tissue: Lung.
[12]"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.
[13]"Molecular model of human beta-cell glucokinase built by analogy to the crystal structure of yeast hexokinase B."
St Charles R., Harrison R.W., Bell G.I., Pilkis S.J., Weber I.T.
Diabetes 43:784-791(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: 3D-STRUCTURE MODELING.
[14]"Structural basis for allosteric regulation of the monomeric allosteric enzyme human glucokinase."
Kamata K., Mitsuya M., Nishimura T., Eiki J., Nagata Y.
Structure 12:429-438(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 16-465 OF APOPROTEIN AND IN COMPLEX WITH GLUCOSE, SUBUNIT, ENZYME REGULATION.
[15]"Discovery of novel 3,6-disubstituted 2-pyridinecarboxamide derivatives as GK activators."
Mitsuya M., Kamata K., Bamba M., Watanabe H., Sasaki Y., Sasaki K., Ohyama S., Hosaka H., Nagata Y., Eiki J., Nishimura T.
Bioorg. Med. Chem. Lett. 19:2718-2721(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 16-465 IN COMPLEX WITH SYNTHETIC ALLOSTERIC ACTIVATOR.
[16]"Structural basis for regulation of human glucokinase by glucokinase regulatory protein."
Beck T., Miller B.G.
Biochemistry 52:6232-6239(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.4 ANGSTROMS) OF 3-465 IN COMPLEX WITH RAT GKRP.
[17]"Missense glucokinase mutation in maturity-onset diabetes of the young and mutation screening in late-onset diabetes."
Stoffel M., Patel P., Lo Y.-M.D., Hattersley A.T., Lucassen A.M., Page R., Bell J.I., Bell G.I., Turner R.C., Wainscoat J.S.
Nat. Genet. 2:153-156(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MODY2 ARG-299.
[18]"Glucokinase gene variants in the common form of NIDDM."
Chiu K.C., Tanizawa Y., Permutt M.A.
Diabetes 42:579-582(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT THR-11.
[19]"Identification of glucokinase mutations in subjects with gestational diabetes mellitus."
Stoffel M., Bell K.L., Blackburn C.L., Powell K.L., Seo T.S., Takeda J., Vionnet N., Xiang K.-S., Gidh-Jain M., Pilkis S.J., Ober C., Bell G.I.
Diabetes 42:937-940(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MODY2 PRO-131.
[20]"Structure/function studies of human beta-cell glucokinase. Enzymatic properties of a sequence polymorphism, mutations associated with diabetes, and other site-directed mutants."
Takeda J., Gidh-Jain M., Xu L.Z., Froguel P., Velho G., Vaxillaire M., Cohen D., Shimada F., Makino H., Nishi S., Stoffel M., Vionnet N., St Charles R., Harrison R.W., Weber I.T., Bell G.I., Pilkis S.J.
J. Biol. Chem. 268:15200-15204(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ASN-4, VARIANTS MODY2 LYS-70; PRO-131; THR-188; ARG-257 AND GLU-414.
[21]"Glucokinase mutations associated with non-insulin-dependent (type 2) diabetes mellitus have decreased enzymatic activity: implications for structure/function relationships."
Gidh-Jain M., Takeda J., Xu L.Z., Lange A.J., Vionnet N., Stoffel M., Froguel P., Velho G., Sun D., Cohen D., Patel P., Lo Y.-M.D., Hattersley A.T., Luthman H., Wedell A., St Charles R., Harrison R.W., Weber I.T., Bell G.I., Pilkis S.J.
Proc. Natl. Acad. Sci. U.S.A. 90:1932-1936(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS MODY2.
[22]"Six mutations in the glucokinase gene identified in MODY by using a nonradioactive sensitive screening technique."
Hager J., Blanche H., Sun F., Vionnet N., Vaxillaire M., Poller W., Cohen D., Czernichow P., Velho G., Robert J.-J., Cohen N., Froguel P.
Diabetes 43:730-733(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MODY2 TRP-36; MET-209 AND GLU-261.
[23]"Identification of 14 new glucokinase mutations and description of the clinical profile of 42 MODY-2 families."
Velho G., Blanche H., Vaxillaire M., Bellanne-Chantelot C., Pardini V.C., Timsit J., Passa P., Deschamps I., Robert J.-J., Weber I.T., Marotta D., Pilkis S.J., Lipkind G.M., Bell G.I., Froguel P.
Diabetologia 40:217-224(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MODY2.
[24]"Three novel missense mutations in the glucokinase gene (G80S; E221K; G227C) in Italian subjects with maturity-onset diabetes of the young (MODY)."
Guazzini B., Gaffi D., Mainieri D., Multari G., Cordera R., Bertolini S., Pozza G., Meschi F., Barbetti F.
Hum. Mutat. 12:136-136(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MODY2 SER-80; LYS-221 AND CYS-227.
[25]"Mutations in the glucokinase gene of the fetus result in reduced birth weight."
Hattersley A.T., Beards F., Ballantyne E., Appleton M., Harvey R., Ellard S.
Nat. Genet. 19:268-270(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MODY2 HIS-108; SER-150; THR-259; ARG-299; TYR-382; THR-384 AND CYS-392.
[26]"Familial hyperinsulinism caused by an activating glucokinase mutation."
Glaser B., Kesavan P., Heyman M., Davis E., Cuesta A., Buchs A., Stanley C.A., Thornton P.S., Permutt M.A., Matschinsky F.M., Herold K.C.
N. Engl. J. Med. 338:226-230(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HHF3 MET-455.
[27]"Molecular genetics of diabetes mellitus in Chinese subjects: identification of mutations in glucokinase and hepatocyte nuclear factor-1alpha genes in patients with early-onset type 2 diabetes mellitus/MODY."
Ng M.C.Y., Cockburn B.N., Lindner T.H., Yeung V.T.F., Chow C.-C., So W.-Y., Li J.K.Y., Lo Y.M.D., Lee Z.S.K., Cockram C.S., Critchley J.A.J.H., Bell G.I., Chan J.C.N.
Diabet. Med. 16:956-963(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MODY2 THR-110; ASP-119 AND VAL-385.
[28]"Identification of glucokinase mutation in subjects with post-renal transplantation diabetes mellitus."
Nam J.H., Lee H.C., Kim Y.H., Cha B.S., Song Y.D., Lim S.K., Kim K.R., Huh K.B.
Diabetes Res. Clin. Pract. 50:169-176(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MODY2 PRO-164.
[29]"Neonatal diabetes mellitus due to complete glucokinase deficiency."
Njoelstad P.R., Soevik O., Cuesta-Munoz A., Bjoerkhaug L., Massa O., Barbetti F., Undlien D.E., Shiota C., Magnuson M.A., Molven A., Matschinsky F.M., Bell G.I.
N. Engl. J. Med. 344:1588-1592(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MODY2 LYS-210 AND MET-228.
[30]"The previously reported T342P GCK missense variant is not a pathogenic mutation causing MODY."
Steele A.M., Tribble N.D., Caswell R., Wensley K.J., Hattersley A.T., Gloyn A.L., Ellard S.
Diabetologia 54:2202-2205(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PRO-342.
+Additional computationally mapped references.

Web resources

Wikipedia

Glucokinase entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M88011 mRNA. Translation: AAA51824.1.
M69051 mRNA. Translation: AAB59563.1. Sequence problems.
M90298 Genomic DNA. Translation: AAA67541.1. Different termination.
M90298 Genomic DNA. Translation: AAA67542.1. Different termination.
M90299 mRNA. Translation: AAA52562.1.
AF041022 expand/collapse EMBL AC list , AF041012, AF041015, AF041016, AF041017, AF041018, AF041019, AF041020, AF041021 Genomic DNA. Translation: AAB97680.1.
AF041022 expand/collapse EMBL AC list , AF041013, AF041015, AF041016, AF041017, AF041018, AF041019, AF041020, AF041021 Genomic DNA. Translation: AAB97681.1.
AF041022 expand/collapse EMBL AC list , AF041014, AF041015, AF041016, AF041017, AF041018, AF041019, AF041020, AF041021 Genomic DNA. Translation: AAB97682.1.
AK122876 mRNA. Translation: BAG53774.1.
CH236960 Genomic DNA. Translation: EAL23765.1.
CH236960 Genomic DNA. Translation: EAL23766.1.
CH471128 Genomic DNA. Translation: EAW61114.1.
CH471128 Genomic DNA. Translation: EAW61116.1.
BC001890 mRNA. Translation: AAH01890.1.
CCDSCCDS5479.1. [P35557-1]
CCDS5480.1. [P35557-2]
CCDS5481.1. [P35557-3]
PIRA46157.
B46157.
C46157.
RefSeqNP_000153.1. NM_000162.3. [P35557-1]
NP_277042.1. NM_033507.1. [P35557-2]
NP_277043.1. NM_033508.1. [P35557-3]
UniGeneHs.1270.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1GLKmodel-A1-465[»]
1V4SX-ray2.30A16-465[»]
1V4TX-ray3.40A16-465[»]
3A0IX-ray2.20X16-465[»]
3F9MX-ray1.50A12-465[»]
3FGUX-ray2.15A12-465[»]
3FR0X-ray2.70A16-465[»]
3GOIX-ray2.52A16-465[»]
3H1VX-ray2.11X16-465[»]
3ID8X-ray2.40A12-465[»]
3IDHX-ray2.14A12-465[»]
3IMXX-ray2.00A16-465[»]
3QICX-ray2.20A12-465[»]
3S41X-ray2.18A12-465[»]
3VEVX-ray1.80A12-465[»]
3VEYX-ray2.25A16-465[»]
3VF6X-ray1.86A12-465[»]
4DCHX-ray1.79A1-465[»]
4DHYX-ray2.38A12-465[»]
4ISEX-ray1.78A16-465[»]
4ISFX-ray2.09A16-465[»]
4ISGX-ray2.64A16-465[»]
4IWVX-ray2.10A16-465[»]
4IXCX-ray2.00A16-465[»]
4L3QX-ray2.70A16-465[»]
4LC9X-ray3.40B3-465[»]
4MLEX-ray2.60A16-465[»]
4MLHX-ray2.90A16-465[»]
ProteinModelPortalP35557.
SMRP35557. Positions 16-460.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108915. 4 interactions.
IntActP35557. 5 interactions.
STRING9606.ENSP00000223366.

Chemistry

BindingDBP35557.
ChEMBLCHEMBL3820.

PTM databases

PhosphoSiteP35557.

Polymorphism databases

DMDM547696.

Proteomic databases

PaxDbP35557.
PRIDEP35557.

Protocols and materials databases

DNASU2645.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000345378; ENSP00000223366; ENSG00000106633. [P35557-2]
ENST00000395796; ENSP00000379142; ENSG00000106633. [P35557-3]
ENST00000403799; ENSP00000384247; ENSG00000106633. [P35557-1]
GeneID2645.
KEGGhsa:2645.
UCSCuc003tkj.1. human. [P35557-3]
uc003tkk.1. human. [P35557-2]
uc003tkl.2. human. [P35557-1]

Organism-specific databases

CTD2645.
GeneCardsGC07M044183.
GeneReviewsGCK.
HGNCHGNC:4195. GCK.
HPAHPA007034.
HPA007093.
MIM125851. phenotype.
138079. gene.
602485. phenotype.
606391. phenotype.
neXtProtNX_P35557.
Orphanet79299. Hyperinsulinism due to glucokinase deficiency.
552. MODY syndrome.
99885. Permanent neonatal diabetes mellitus.
PharmGKBPA28610.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5026.
HOGENOMHOG000162670.
HOVERGENHBG000142.
InParanoidP35557.
KOK12407.
OMAEDHQCEV.
PhylomeDBP35557.
TreeFamTF314238.

Enzyme and pathway databases

BioCycMetaCyc:HS02935-MONOMER.
ReactomeREACT_111045. Developmental Biology.
REACT_111217. Metabolism.
REACT_116125. Disease.
REACT_15518. Transmembrane transport of small molecules.
SABIO-RKP35557.

Gene expression databases

ArrayExpressP35557.
BgeeP35557.
CleanExHS_GCK.
GenevestigatorP35557.

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

EvolutionaryTraceP35557.
GeneWikiGlucokinase.
GenomeRNAi2645.
NextBio10434.
PROP35557.
SOURCESearch...

Entry information

Entry nameHXK4_HUMAN
AccessionPrimary (citable) accession number: P35557
Secondary accession number(s): A4D2J2, A4D2J3, Q05810
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: July 9, 2014
This is version 159 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM