P35557 (HXK4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:

GCK

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	465 AA.
Sequence status	Complete.
Protein existence	Evidence 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. Ref.13
Subunit structure	Monomer. Ref.13
Tissue specificity	Isoform 1 is expressed in pancreas. Isoform 2 and isoform 3 is expressed in liver.
Involvement in disease	Defects in GCK are the cause of maturity-onset diabetes of the young type 2 (MODY2) [MIM:125851]; also shortened MODY-2. MODY is 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. Ref.5 Ref.7 Ref.15 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.25 Ref.26 Ref.27 Defects in GCK are the cause of familial hyperinsulinemic hypoglycemia type 3 (HHF3) [MIM:602485]; also known as persistent hyperinsulinemic hypoglycemia of infancy (PHHI) or congenital hyperinsulinism. HHF is the most common cause of persistent hypoglycemia in infancy. Unless early and aggressive intervention is undertaken, brain damage from recurrent episodes of hypoglycemia may occur. Ref.24
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 process	Glycolysis
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Diabetes mellitus Disease mutation
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase
Technical term	3D-structure Allosteric enzyme Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	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. Source: UniProtKB endocrine pancreas development Traceable author statement. Source: Reactome glucose homeostasis Inferred from mutant phenotype. Source: UniProtKB glucose transport Traceable author statement. Source: Reactome glycolysis Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of gluconeogenesis Inferred from mutant phenotype. Source: UniProtKB positive regulation of glycogen biosynthetic process Inferred from mutant phenotype. Source: UniProtKB positive regulation of insulin secretion Inferred from mutant phenotype. Source: UniProtKB regulation of glucose transport Traceable author statement. Source: Reactome regulation of glycolysis Non-traceable author statement. Source: BHF-UCL transmembrane transport Traceable author statement. Source: Reactome
Cellular component	cytosol Traceable author statement. Source: Reactome nucleoplasm Traceable author statement. Source: Reactome
Molecular function	ATP binding Inferred from direct assay Ref.19. Source: UniProtKB glucokinase activity Inferred from direct assay Ref.19. Source: UniProtKB glucose binding Inferred from direct assay Ref.19. Source: UniProtKB protein binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
GCKR	Q14397	2	EBI-709928,EBI-709948
PFKFB1	P16118	2	EBI-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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 465

465

Glucokinase

PRO_0000197593

Regions

Nucleotide binding

78 – 83

6

ATP By similarity

Nucleotide binding

295 – 296

2

ATP By similarity

Nucleotide binding

332 – 336

5

ATP By similarity

Nucleotide binding

411 – 415

5

ATP By similarity

Region

151 – 152

2

Substrate binding

Region

168 – 169

2

Substrate binding

Region

204 – 205

2

Substrate binding

Sites

Binding site

104

1

ATP Potential

Binding site

228

1

ATP By similarity

Binding site

231

1

Substrate

Binding site

256

1

Substrate

Binding site

290

1

Substrate

Natural variations

Alternative sequence

1 – 15

15

MLDDR…AKKEK → MAMDVTRSQAQTALTL in isoform 2.

VSP_002074

Alternative sequence

1 – 15

15

MLDDR…AKKEK → MPRPRSQLPQPNSQ in isoform 3.

VSP_002075

Natural variant

4

1

D → N. Ref.18

VAR_003692

Natural variant

11

1

A → T. Ref.16

VAR_010583

Natural variant

36

1

R → W in MODY2. Ref.20

VAR_010584

Natural variant

53

1

A → S in MODY2.

VAR_010585

Natural variant

70

1

E → K in MODY2; large increase in Km for glucose. Ref.18

VAR_003693

Natural variant

80

1

G → A in MODY2.

VAR_003694

Natural variant

80

1

G → S in MODY2. Ref.22

VAR_003695

Natural variant

107

1

M → T. Ref.2 Ref.7

VAR_003696

Natural variant

108

1

Y → H in MODY2. Ref.23

VAR_010586

Natural variant

110

1

I → T in MODY2. Ref.25

VAR_012352

Natural variant

119

1

A → D in MODY2. Ref.25

VAR_012353

Natural variant

131

1

S → P in MODY2; significant increase in the Km and in the affinity for ATP. Ref.17 Ref.18

VAR_003697

Natural variant

137

1

H → R in MODY2.

VAR_010587

Natural variant

150

1

F → S in MODY2. Ref.23

VAR_010588

Natural variant

164

1

L → P in MODY2. Ref.26

VAR_012350

Natural variant

168

1

T → P in MODY2.

VAR_010589

Natural variant

175

1

G → R in MODY2.

VAR_003698

Natural variant

182

1

V → M in MODY2.

VAR_003699

Natural variant

188

1

A → T in MODY2; large increase in Km for glucose. Ref.18

VAR_003700

Natural variant

203

1

V → A in MODY2.

VAR_003701

Natural variant

209

1

T → M in MODY2. Ref.20

VAR_010590

Natural variant

210

1

M → K in MODY2. Ref.27

VAR_012351

Natural variant

210

1

M → T in MODY2.

VAR_010591

Natural variant

213

1

C → R in MODY2.

VAR_010592

Natural variant

221

1

E → K in MODY2. Ref.22

VAR_003702

Natural variant

226

1

V → M in MODY2.

VAR_003703

Natural variant

227

1

G → C in MODY2. Ref.22

VAR_003704

Natural variant

228

1

T → M in MODY2. Ref.5 Ref.27

VAR_003705

Natural variant

256

1

E → K in MODY2.

VAR_003706

Natural variant

257

1

W → R in MODY2; almost complete loss of activity. Ref.18

VAR_003707

Natural variant

259

1

A → T in MODY2. Ref.23

VAR_010593

Natural variant

261

1

G → E in MODY2. Ref.20

VAR_010594

Natural variant

261

1

G → R in MODY2. Ref.5 Ref.7

VAR_003708

Natural variant

279

1

E → Q in MODY2.

VAR_003709

Natural variant

299

1

G → R in MODY2. Ref.15 Ref.23

VAR_003710

Natural variant

300

1

E → K in MODY2.

VAR_003712

Natural variant

300

1

E → Q in MODY2.

VAR_003711

Natural variant

309

1

L → P in MODY2.

VAR_003713

Natural variant

336

1

S → L in MODY2.

VAR_010595

Natural variant

342

1

T → P. Ref.28

VAR_066615

Natural variant

367

1

V → M in MODY2.

VAR_010596

Natural variant

382

1

C → Y in MODY2. Ref.23

VAR_010597

Natural variant

384

1

A → T in MODY2. Ref.23

VAR_010598

Natural variant

385

1

G → V in MODY2. Ref.25

VAR_012354

Natural variant

392

1

R → C in MODY2. Ref.23

VAR_010599

Natural variant

414

1

K → E in MODY2; large increase in Km for glucose. Ref.18

VAR_003714

Natural variant

455

1

V → M in HHF3. Ref.24

VAR_003715

Experimental info

Mutagenesis

177

1

E → K: Small change in activity.

Mutagenesis

256

1

E → A: Inactive enzyme.

Mutagenesis

414

1

K → A: Small change in activity.

Secondary structure

1

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465

Helix Strand Turn

Details...

Helix

16 – 20

5

Helix

21 – 23

3

Helix

27 – 45

19

Turn

47 – 52

6

Beta strand

58 – 64

7

Beta strand

72 – 91

20

Beta strand

95 – 97

3

Beta strand

100 – 109

10

Turn

113 – 115

3

Beta strand

116 – 118

3

Helix

119 – 135

17

Turn

136 – 138

3

Beta strand

145 – 150

6

Beta strand

154 – 158

5

Beta strand

161 – 164

4

Helix

181 – 189

9

Turn

190 – 192

3

Beta strand

198 – 203

6

Helix

205 – 214

10

Beta strand

220 – 237

18

Helix

238 – 240

3

Beta strand

248 – 254

7

Helix

257 – 259

3

Turn

260 – 263

4

Turn

265 – 269

5

Helix

272 – 279

8

Beta strand

281 – 283

3

Helix

288 – 293

6

Turn

295 – 297

3

Helix

298 – 311

14

Helix

316 – 318

3

Helix

323 – 325

3

Helix

332 – 338

7

Beta strand

343 – 345

3

Helix

346 – 354

9

Helix

361 – 394

34

Beta strand

399 – 409

11

Helix

411 – 415

5

Helix

419 – 430

12

Beta strand

434 – 440

7

Helix

444 – 460

17

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 1, 1994. Version 1. Checksum: 094D4A2F78096724	FASTA	465	52,191
	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
	Isoform 2 [UniParc]. Checksum: A44B768452105627	FASTA	466	52,136
	10 20 30 40 50 60 MAMDVTRSQA QTALTLVEQI LAEFQLQEED LKKVMRRMQK EMDRGLRLET HEEASVKMLP 70 80 90 100 110 120 TYVRSTPEGS EVGDFLSLDL GGTNFRVMLV KVGEGEEGQW SVKTKHQMYS IPEDAMTGTA 130 140 150 160 170 180 EMLFDYISEC ISDFLDKHQM KHKKLPLGFT FSFPVRHEDI DKGILLNWTK GFKASGAEGN 190 200 210 220 230 240 NVVGLLRDAI KRRGDFEMDV VAMVNDTVAT MISCYYEDHQ CEVGMIVGTG CNACYMEEMQ 250 260 270 280 290 300 NVELVEGDEG RMCVNTEWGA FGDSGELDEF LLEYDRLVDE SSANPGQQLY EKLIGGKYMG 310 320 330 340 350 360 ELVRLVLLRL VDENLLFHGE ASEQLRTRGA FETRFVSQVE SDTGDRKQIY NILSTLGLRP 370 380 390 400 410 420 STTDCDIVRR ACESVSTRAA HMCSAGLAGV INRMRESRSE DVMRITVGVD GSVYKLHPSF 430 440 450 460 KERFHASVRR LTPSCEITFI ESEEGSGRGA ALVSAVACKK ACMLGQ
	Isoform 3 [UniParc]. Checksum: 5FA1020BBF98A4E9	FASTA	464	52,035
	10 20 30 40 50 60 MPRPRSQLPQ PNSQVEQILA EFQLQEEDLK KVMRRMQKEM DRGLRLETHE EASVKMLPTY 70 80 90 100 110 120 VRSTPEGSEV GDFLSLDLGG TNFRVMLVKV GEGEEGQWSV KTKHQMYSIP EDAMTGTAEM 130 140 150 160 170 180 LFDYISECIS DFLDKHQMKH KKLPLGFTFS FPVRHEDIDK GILLNWTKGF KASGAEGNNV 190 200 210 220 230 240 VGLLRDAIKR RGDFEMDVVA MVNDTVATMI SCYYEDHQCE VGMIVGTGCN ACYMEEMQNV 250 260 270 280 290 300 ELVEGDEGRM CVNTEWGAFG DSGELDEFLL EYDRLVDESS ANPGQQLYEK LIGGKYMGEL 310 320 330 340 350 360 VRLVLLRLVD ENLLFHGEAS EQLRTRGAFE TRFVSQVESD TGDRKQIYNI LSTLGLRPST 370 380 390 400 410 420 TDCDIVRRAC ESVSTRAAHM CSAGLAGVIN RMRESRSEDV MRITVGVDGS VYKLHPSFKE 430 440 450 460 RFHASVRRLT PSCEITFIES EEGSGRGAAL VSAVACKKAC MLGQ

References

	« Hide 'large scale' referencesShow '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: 1354840] [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: 1871135] [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: 1511800] [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: 1612194] [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: 1502186] [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: 1464666] [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. , 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: 14702039] [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. , 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: 12690205] [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. , 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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung.
[12]	"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: 8194664] [Abstract] Cited for: 3D-STRUCTURE MODELING.
[13]	"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: 15016359] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 16-465 OF APOPROTEIN AND IN COMPLEX WITH GLUCOSE, SUBUNIT, ENZYME REGULATION.
[14]	"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: 19362831] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 16-465 IN COMPLEX WITH SYNTHETIC ALLOSTERIC ACTIVATOR.
[15]	"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: 1303265] [Abstract] Cited for: VARIANT MODY2 ARG-299.
[16]	"Glucokinase gene variants in the common form of NIDDM." Chiu K.C., Tanizawa Y., Permutt M.A. Diabetes 42:579-582(1993) [PubMed: 8454109] [Abstract] Cited for: VARIANT THR-11.
[17]	"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: 8495817] [Abstract] Cited for: VARIANT MODY2 PRO-131.
[18]	"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: 8325892] [Abstract] Cited for: VARIANT ASN-4, VARIANTS MODY2 LYS-70; PRO-131; THR-188; ARG-257 AND GLU-414.
[19]	"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: 8446612] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS MODY2.
[20]	"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: 8168652] [Abstract] Cited for: VARIANTS MODY2 TRP-36; MET-209 AND GLU-261.
[21]	"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: 9049484] [Abstract] Cited for: VARIANTS MODY2.
[22]	"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: 10694920] [Abstract] Cited for: VARIANTS MODY2 SER-80; LYS-221 AND CYS-227.
[23]	"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: 9662401] [Abstract] Cited for: VARIANTS MODY2 HIS-108; SER-150; THR-259; ARG-299; TYR-382; THR-384 AND CYS-392.
[24]	"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: 9435328] [Abstract] Cited for: VARIANT HHF3 MET-455.
[25]	"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: 10588527] [Abstract] Cited for: VARIANTS MODY2 THR-110; ASP-119 AND VAL-385.
[26]	"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: 11106831] [Abstract] Cited for: VARIANT MODY2 PRO-164.
[27]	"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: 11372010] [Abstract] Cited for: VARIANTS MODY2 LYS-210 AND MET-228.
[28]	"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: 21604084] [Abstract] Cited for: VARIANT PRO-342.
+	Additional computationally mapped references.

Web resources

GeneReviews

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 , AF041012, AF041015, AF041016, AF041017, AF041018, AF041019, AF041020, AF041021 Genomic DNA. Translation: AAB97680.1.
AF041022 , AF041013, AF041015, AF041016, AF041017, AF041018, AF041019, AF041020, AF041021 Genomic DNA. Translation: AAB97681.1.
AF041022 , 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.

IPI

IPI00218767.
IPI00218768.
IPI00244083.

PIR

A46157.
B46157.
C46157.

RefSeq

NP_000153.1. NM_000162.3.
NP_277042.1. NM_033507.1.
NP_277043.1. NM_033508.1.

UniGene

Hs.1270.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1GLK	model	-	A	1-465	[»]
1V4S	X-ray	2.30	A	16-465	[»]
1V4T	X-ray	3.40	A	16-465	[»]
3A0I	X-ray	2.20	X	16-465	[»]
3F9M	X-ray	1.50	A	12-465	[»]
3FGU	X-ray	2.15	A	12-465	[»]
3FR0	X-ray	2.70	A	16-465	[»]
3GOI	X-ray	2.52	A	16-465	[»]
3H1V	X-ray	2.11	X	16-465	[»]
3ID8	X-ray	2.40	A	12-465	[»]
3IDH	X-ray	2.14	A	12-465	[»]
3IMX	X-ray	2.00	A	16-465	[»]
3QIC	X-ray	2.20	A	12-465	[»]
3S41	X-ray	2.18	A	12-465	[»]

ProteinModelPortal

P35557.

SMR

P35557. Positions 16-460.

ModBase

Search...

Protein-protein interaction databases

IntAct

P35557. 5 interactions.

STRING

P35557.

PTM databases

PhosphoSite

P35557.

Polymorphism databases

DMDM

547696.

Proteomic databases

PRIDE

P35557.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000403799; ENSP00000384247; ENSG00000106633.

GeneID

2645.

KEGG

hsa:2645.

UCSC

uc003tkj.1. human.
uc003tkk.1. human.
uc003tkl.2. human.

Organism-specific databases

CTD

2645.

GeneCards

GC07M044183.

H-InvDB

HIX0006646.

HGNC

HGNC:4195. GCK.

HPA

HPA007034.
HPA007093.

MIM

125851. phenotype.
138079. gene.
602485. phenotype.
606391. phenotype.

neXtProt

NX_P35557.

Orphanet

79299. Hyperinsulinism due to glucokinase deficiency.
552. MODY syndrome.
99885. Permanent neonatal diabetes mellitus.

PharmGKB

PA28610.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

HBG522186.

HOVERGEN

HBG000142.

InParanoid

P35557.

OMA

EDHQCEV.

PhylomeDB

P35557.

Enzyme and pathway databases

BioCyc

MetaCyc:MONOMER-13391.

Pathway_Interaction_DB

hnf3bpathway. FOXA2 and FOXA3 transcription factor networks.
hif1_tfpathway. HIF-1-alpha transcription factor network.

Reactome

REACT_111045. Developmental Biology.
REACT_15518. Transmembrane transport of small molecules.
REACT_474. Metabolism of carbohydrates.

Gene expression databases

ArrayExpress

P35557.

Bgee

P35557.

CleanEx

HS_GCK.

Genevestigator

P35557.

GermOnline

ENSG00000106633. Homo sapiens.

Family and domain databases

InterPro

IPR001312. Hexokinase.
IPR022673. Hexokinase_C.
IPR019807. Hexokinase_CS.
IPR022672. Hexokinase_N.
[Graphical view]

KO

K12407.

PANTHER

PTHR19443. Hexokinase. 1 hit.

Pfam

PF00349. Hexokinase_1. 1 hit.
PF03727. Hexokinase_2. 1 hit.
[Graphical view]

PRINTS

PR00475. HEXOKINASE.

PROSITE

PS00378. HEXOKINASES. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

10434.

SOURCE

Search...

Entry information

Entry name

HXK4_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 132 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.