NameGlucokinase
Synonyms
  • 2.7.1.2
  • Hexokinase type IV
  • Hexokinase-4
  • Hexokinase-D
  • HK IV
  • HK4
Gene NameGCK
OrganismHuman
Amino acid sequence
>lcl|BSEQ0002103|Glucokinase
MLDDRARMEAAKKEKVEQILAEFQLQEEDLKKVMRRMQKEMDRGLRLETHEEASVKMLPT
YVRSTPEGSEVGDFLSLDLGGTNFRVMLVKVGEGEEGQWSVKTKHQMYSIPEDAMTGTAE
MLFDYISECISDFLDKHQMKHKKLPLGFTFSFPVRHEDIDKGILLNWTKGFKASGAEGNN
VVGLLRDAIKRRGDFEMDVVAMVNDTVATMISCYYEDHQCEVGMIVGTGCNACYMEEMQN
VELVEGDEGRMCVNTEWGAFGDSGELDEFLLEYDRLVDESSANPGQQLYEKLIGGKYMGE
LVRLVLLRLVDENLLFHGEASEQLRTRGAFETRFVSQVESDTGDRKQIYNILSTLGLRPS
TTDCDIVRRACESVSTRAAHMCSAGLAGVINRMRESRSEDVMRITVGVDGSVYKLHPSFK
ERFHASVRRLTPSCEITFIESEEGSGRGAALVSAVACKKACMLGQ
Number of residues465
Molecular Weight52191.07
Theoretical pI4.85
GO Classification
Functions
  • glucose binding
  • ATP binding
  • glucokinase activity
Processes
  • cellular glucose homeostasis
  • NADP metabolic process
  • positive regulation of glycogen biosynthetic process
  • carbohydrate metabolic process
  • hexose transport
  • glucose homeostasis
  • regulation of glucose transport
  • glucose metabolic process
  • negative regulation of gluconeogenesis
  • regulation of glycolytic process
  • transmembrane transport
  • regulation of insulin secretion
  • glucose 6-phosphate metabolic process
  • cellular response to insulin stimulus
  • cellular response to leptin stimulus
  • glycolytic process
  • detection of glucose
  • canonical glycolysis
  • endocrine pancreas development
  • positive regulation of insulin secretion
  • calcium ion import
  • regulation of potassium ion transport
  • glucose transport
  • small molecule metabolic process
Components
  • cytosol
  • nucleoplasm
  • mitochondrion
General FunctionGlucose binding
Specific FunctionCatalyzes 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.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID179427
UniProtKB IDP35557
UniProtKB Entry NameHXK4_HUMAN
Cellular LocationCytoplasm
Gene sequence
>lcl|BSEQ0016300|Glucokinase (GCK)
ATGCTGGACGACAGAGCCAGGATGGAGGCCGCCAAGAAGGAGAAGGTAGAGCAGATCCTG
GCAGAGTTCCAGCTGCAGGAGGAGGACCTGAAGAAGGTGATGAGACGGATGCAGAAGGAG
ATGGACCGCGGCCTGAGGCTGGAGACCCATGAAGAGGCCAGTGTGAAGATGCTGCCCACC
TACGTGCGCTCCACCCCAGAAGGCTCAGAAGTCGGGGACTTCCTCTCCCTGGACCTGGGT
GGCACTAACTTCAGGGTGATGCTGGTGAAGGTGGGAGAAGGTGAGGAGGGGCAGTGGAGC
GTGAAGACCAAACACCAGATGTACTCCATCCCCGAGGACGCCATGACCGGCACTGCTGAG
ATGCTCTTCGACTACATCTCTGAGTGCATCTCCGACTTCCTGGACAAGCATCAGATGAAA
CACAAGAAGCTGCCCCTGGGCTTCACCTTCTCCTTTCCTGTGAGGCACGAAGACATCGAT
AAGGGCATCCTTCTCAACTGGACCAAGGGCTTCAAGGCCTCAGGAGCAGAAGGGAACAAT
GTCGTGGGGCTTCTGCGAGACGCTATCAAACGGAGAGGGGACTTTGAAATGGATGTGGTG
GCAATGGTGAATGACACGGTGGCCACGATGATCTCCTGCTACTACGAAGACCATCAGTGC
GAGGTCGGCATGATCGTGGGCACGGGCTGCAATGCCTGCTACATGGAGGAGATGCAGAAT
GTGGAGCTGGTGGAGGGGGACGAGGGCCGCATGTGCGTCAATACCGAGTGGGGCGCCTTC
GGGGACTCCGGCGAGCTGGACGAGTTCCTGCTGGAGTATGACCGCCTGGTGGACGAGAGC
TCTGCAAACCCCGGTCAGCAGCTGTATGAGAAGCTCATAGGTGGCAAGTACATGGGCGAG
CTGGTGCGGCTTGTGCTGCTCAGGCTCGTGGACGAAAACCTGCTCTTCCACGGGGAGGCC
TCCGAGCAGCTGCGCACACGCGGAGCCTTCGAGACGCGCTTCGTGTCGCAGGTGGAGAGC
GACACGGGCGACCGCAAGCAGATCTACAACATCCTGAGCACGCTGGGGCTGCGACCCTCG
ACCACCGACTGCGACATCGTGCGCCGCGCCTGCGAGAGCGTGTCTACGCGCGCTGCGCAC
ATGTGCTCGGCGGGGCTGGCGGGCGTCATCAACCGCATGCGCGAGAGCCGCAGCGAGGAC
GTAATGCGCATCACTGTGGGCGTGGATGGCTCCGTGTACAAGCTGCACCCCAGCTTCAAG
GAGCGGTTCCATGCCAGCGTGCGCAGGCTGACGCCCAGCTGCGAGATCACCTTCATCGAG
TCGGAGGAGGGCAGTGGCCGGGGCGCGGCCCTGGTCTCGGCGGTGGCCTGTAAGAAGGCC
TGTATGCTGGGCCAGTGA
GenBank Gene IDM88011
GeneCard IDNot Available
GenAtlas IDGCK
HGNC IDHGNC:4195
Chromosome Location7
Locus7p15.3-p15.1
References
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  2. Tanizawa Y, Koranyi LI, Welling CM, Permutt MA: Human liver glucokinase gene: cloning and sequence determination of two alternatively spliced cDNAs. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7294-7. 1871135
  3. Nishi S, Stoffel M, Xiang K, Shows TB, Bell GI, Takeda J: Human pancreatic beta-cell glucokinase: cDNA sequence and localization of the polymorphic gene to chromosome 7, band p 13. Diabetologia. 1992 Aug;35(8):743-7. 1511800
  4. Koranyi LI, Tanizawa Y, Welling CM, Rabin DU, Permutt MA: Human islet glucokinase gene. Isolation and sequence analysis of full-length cDNA. Diabetes. 1992 Jul;41(7):807-11. 1612194
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  11. St Charles R, Harrison RW, Bell GI, Pilkis SJ, Weber IT: Molecular model of human beta-cell glucokinase built by analogy to the crystal structure of yeast hexokinase B. Diabetes. 1994 Jun;43(6):784-91. 8194664
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  22. Guazzini B, Gaffi D, Mainieri D, Multari G, Cordera R, Bertolini S, Pozza G, Meschi F, Barbetti F: Three novel missense mutations in the glucokinase gene (G80S; E221K; G227C) in Italian subjects with maturity-onset diabetes of the young (MODY). Mutations in brief no. 162. Online. Hum Mutat. 1998;12(2):136. 10694920
  23. Hattersley AT, Beards F, Ballantyne E, Appleton M, Harvey R, Ellard S: Mutations in the glucokinase gene of the fetus result in reduced birth weight. Nat Genet. 1998 Jul;19(3):268-70. 9662401
  24. Glaser B, Kesavan P, Heyman M, Davis E, Cuesta A, Buchs A, Stanley CA, Thornton PS, Permutt MA, Matschinsky FM, Herold KC: Familial hyperinsulinism caused by an activating glucokinase mutation. N Engl J Med. 1998 Jan 22;338(4):226-30. 9435328
  25. Ng MC, Cockburn BN, Lindner TH, Yeung VT, Chow CC, So WY, Li JK, Lo YM, Lee ZS, Cockram CS, Critchley JA, Bell GI, Chan JC: 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. Diabet Med. 1999 Nov;16(11):956-63. 10588527
  26. Nam JH, Lee HC, Kim YH, Cha BS, Song YD, Lim SK, Kim KR, Huh KB: Identification of glucokinase mutation in subjects with post-renal transplantation diabetes mellitus. Diabetes Res Clin Pract. 2000 Dec;50(3):169-76. 11106831
  27. Njolstad PR, Sovik O, Cuesta-Munoz A, Bjorkhaug L, Massa O, Barbetti F, Undlien DE, Shiota C, Magnuson MA, Molven A, Matschinsky FM, Bell GI: Neonatal diabetes mellitus due to complete glucokinase deficiency. N Engl J Med. 2001 May 24;344(21):1588-92. 11372010
  28. Steele AM, Tribble ND, Caswell R, Wensley KJ, Hattersley AT, Gloyn AL, Ellard S: The previously reported T342P GCK missense variant is not a pathogenic mutation causing MODY. Diabetologia. 2011 Aug;54(8):2202-5. doi: 10.1007/s00125-011-2194-5. Epub 2011 May 21. 21604084