Fructose-1,6-bisphosphatase 1

Details

Name
Fructose-1,6-bisphosphatase 1
Synonyms
  • 3.1.3.11
  • D-fructose-1,6-bisphosphate 1-phosphohydrolase 1
  • FBP
  • FBPase 1
  • Liver FBPase
Gene Name
FBP1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0037205|Fructose-1,6-bisphosphatase 1
MADQAPFDTDVNTLTRFVMEEGRKARGTGELTQLLNSLCTAVKAISSAVRKAGIAHLYGI
AGSTNVTGDQVKKLDVLSNDLVMNMLKSSFATCVLVSEEDKHAIIVEPEKRGKYVVCFDP
LDGSSNIDCLVSVGTIFGIYRKKSTDEPSEKDALQPGRNLVAAGYALYGSATMLVLAMDC
GVNCFMLDPAIGEFILVDKDVKIKKKGKIYSLNEGYARDFDPAVTEYIQRKKFPPDNSAP
YGARYVGSMVADVHRTLVYGGIFLYPANKKSPNGKLRLLYECNPMAYVMEKAGGMATTGK
EAVLDVIPTDIHQRAPVILGSPDDVLEFLKVYEKHSAQ
Number of residues
338
Molecular Weight
36842.145
Theoretical pI
6.99
GO Classification
Functions
AMP binding / fructose 1,6-bisphosphate 1-phosphatase activity / identical protein binding / metal ion binding / monosaccharide binding
Processes
carbohydrate metabolic process / cellular response to drug / cellular response to magnesium ion / dephosphorylation / fructose 6-phosphate metabolic process / fructose metabolic process / gluconeogenesis / glucose metabolic process / negative regulation of cell growth / negative regulation of glycolytic process / negative regulation of Ras protein signal transduction / protein homotetramerization / regulation of gluconeogenesis / small molecule metabolic process
Components
cytoplasm / cytosol / extracellular exosome
General Function
Monosaccharide binding
Specific Function
Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the presence of divalent cations, acting as a rate-limiting enzyme in gluconeogenesis. Plays a role in regulating glucose sensing and insulin secretion of pancreatic beta-cells. Appears to modulate glycerol gluconeogenesis in liver. Important regulator of appetite and adiposity; increased expression of the protein in liver after nutrient excess increases circulating satiety hormones and reduces appetite-stimulating neuropeptides and thus seems to provide a feedback mechanism to limit weight gain.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasmic
Gene sequence
>lcl|BSEQ0016789|Fructose-1,6-bisphosphatase 1 (FBP1)
ATGGCTGACCAGGCGCCCTTCGACACGGACGTCAACACCCTGACCCGCTTCGTCATGGAG
GAGGGCAGGAAGGCCCGCGGCACGGGCGAGTTGACCCAGCTGCTCAACTCGCTCTGCACA
GCAGTCAAAGCCATCTCTTCGGCGGTGCGCAAGGCGGGCATCGCGCACCTCTATGGCATT
GCTGGTTCTACCAACGTGACAGGTGATCAAGTTAAGAAGCTGGACGTCCTCTCCAACGAC
CTGGTTATGAACATGTTAAAGTCATCCTTTGCCACGTGTGTTCTCGTGTCAGAAGAAGAT
AAACACGCCATCATAGTGGAACCGGAGAAAAGGGGTAAATATGTGGTCTGTTTTGATCCC
CTTGATGGATCTTCCAACATCGATTGCCTTGTGTCCGTTGGAACCATTTTTGGCATCTAT
AGAAAGAAATCAACTGATGAGCCTTCTGAGAAGGATGCTCTGCAACCAGGCCGGAACCTG
GTGGCAGCCGGCTACGCACTGTATGGCAGTGCCACCATGCTGGTCCTTGCCATGGACTGT
GGGGTCAACTGCTTCATGCTGGACCCGGCCATCGGGGAGTTCATTTTGGTGGACAAGGAT
GTGAAGATAAAAAAGAAAGGTAAAATCTACAGCCTTAACGAGGGCTACGCCAGGGACTTT
GACCCTGCCGTCACTGAGTACATCCAGAGGAAGAAGTTCCCCCCAGATAATTCAGCTCCT
TATGGGGCCCGGTATGTGGGCTCCATGGTGGCTGATGTTCATCGCACTCTGGTCTACGGA
GGGATATTTCTGTACCCCGCTAACAAGAAGAGCCCCAATGGAAAGCTGAGACTGCTGTAC
GAATGCAACCCCATGGCCTACGTCATGGAGAAGGCTGGGGGAATGGCCACCACTGGGAAG
GAGGCCGTGTTAGACGTCATTCCCACAGACATTCACCAGAGGGCGCCGGTGATCTTGGGA
TCCCCCGACGACGTGCTCGAGTTCCTGAAGGTGTATGAGAAGCACTCTGCCCAGTGA
Chromosome Location
9
Locus
9q22.3
External Identifiers
ResourceLink
UniProtKB IDP09467
UniProtKB Entry NameF16P1_HUMAN
GenBank Gene IDL10320
GenAtlas IDFBP1
HGNC IDHGNC:3606
General References
  1. Solomon DH, Raynal MC, Tejwani GA, Cayre YE: Activation of the fructose 1,6-bisphosphatase gene by 1,25-dihydroxyvitamin D3 during monocytic differentiation. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6904-8. [Article]
  2. el-Maghrabi MR, Gidh-Jain M, Austin LR, Pilkis SJ: Isolation of a human liver fructose-1,6-bisphosphatase cDNA and expression of the protein in Escherichia coli. Role of ASP-118 and ASP-121 in catalysis. J Biol Chem. 1993 May 5;268(13):9466-72. [Article]
  3. Kikawa Y, Inuzuka M, Takano T, Shigematsu Y, Nakai A, Yamamoto Y, Jin BY, Koga J, Taketo A, Sudo M: cDNA sequences encoding human fructose 1,6-bisphosphatase from monocytes, liver and kidney: application of monocytes to molecular analysis of human fructose 1,6-bisphosphatase deficiency. Biochem Biophys Res Commun. 1994 Mar 15;199(2):687-93. [Article]
  4. el-Maghrabi MR, Lange AJ, Jiang W, Yamagata K, Stoffel M, Takeda J, Fernald AA, Le Beau MM, Bell GI, Baker L, et al.: Human fructose-1,6-bisphosphatase gene (FBP1): exon-intron organization, localization to chromosome bands 9q22.2-q22.3, and mutation screening in subjects with fructose-1,6-bisphosphatase deficiency. Genomics. 1995 Jun 10;27(3):520-5. [Article]
  5. Skalecki K, Rakus D, Wisniewski JR, Kolodziej J, Dzugaj A: cDNA sequence and kinetic properties of human lung fructose(1, 6)bisphosphatase. Arch Biochem Biophys. 1999 May 1;365(1):1-9. [Article]
  6. Humphray SJ, Oliver K, Hunt AR, Plumb RW, Loveland JE, Howe KL, Andrews TD, Searle S, Hunt SE, Scott CE, Jones MC, Ainscough R, Almeida JP, Ambrose KD, Ashwell RI, Babbage AK, Babbage S, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beasley H, Beasley O, Bird CP, Bray-Allen S, Brown AJ, Brown JY, Burford D, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Chen Y, Clarke G, Clark SY, Clee CM, Clegg S, Collier RE, Corby N, Crosier M, Cummings AT, Davies J, Dhami P, Dunn M, Dutta I, Dyer LW, Earthrowl ME, Faulkner L, Fleming CJ, Frankish A, Frankland JA, French L, Fricker DG, Garner P, Garnett J, Ghori J, Gilbert JG, Glison C, Grafham DV, Gribble S, Griffiths C, Griffiths-Jones S, Grocock R, Guy J, Hall RE, Hammond S, Harley JL, Harrison ES, Hart EA, Heath PD, Henderson CD, Hopkins BL, Howard PJ, Howden PJ, Huckle E, Johnson C, Johnson D, Joy AA, Kay M, Keenan S, Kershaw JK, Kimberley AM, King A, Knights A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd C, Lloyd DM, Lovell J, Martin S, Mashreghi-Mohammadi M, Matthews L, McLaren S, McLay KE, McMurray A, Milne S, Nickerson T, Nisbett J, Nordsiek G, Pearce AV, Peck AI, Porter KM, Pandian R, Pelan S, Phillimore B, Povey S, Ramsey Y, Rand V, Scharfe M, Sehra HK, Shownkeen R, Sims SK, Skuce CD, Smith M, Steward CA, Swarbreck D, Sycamore N, Tester J, Thorpe A, Tracey A, Tromans A, Thomas DW, Wall M, Wallis JM, West AP, Whitehead SL, Willey DL, Williams SA, Wilming L, Wray PW, Young L, Ashurst JL, Coulson A, Blocker H, Durbin R, Sulston JE, Hubbard T, Jackson MJ, Bentley DR, Beck S, Rogers J, Dunham I: DNA sequence and analysis of human chromosome 9. Nature. 2004 May 27;429(6990):369-74. [Article]
  7. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  8. Bertolotti R, Armbruster-Hilbert L, Okayama H: Liver fructose-1,6-bisphosphatase cDNA: trans-complementation of fission yeast and characterization of two human transcripts. Differentiation. 1995 Jul;59(1):51-60. [Article]
  9. Lamont BJ, Visinoni S, Fam BC, Kebede M, Weinrich B, Papapostolou S, Massinet H, Proietto J, Favaloro J, Andrikopoulos S: Expression of human fructose-1,6-bisphosphatase in the liver of transgenic mice results in increased glycerol gluconeogenesis. Endocrinology. 2006 Jun;147(6):2764-72. Epub 2006 Feb 23. [Article]
  10. Zarzycki M, Maciaszczyk E, Dzugaj A: Glu 69 is essential for the high sensitivity of muscle fructose-1,6-bisphosphatase inhibition by calcium ions. FEBS Lett. 2007 Apr 3;581(7):1347-50. Epub 2007 Mar 1. [Article]
  11. Kebede M, Favaloro J, Gunton JE, Laybutt DR, Shaw M, Wong N, Fam BC, Aston-Mourney K, Rantzau C, Zulli A, Proietto J, Andrikopoulos S: Fructose-1,6-bisphosphatase overexpression in pancreatic beta-cells results in reduced insulin secretion: a new mechanism for fat-induced impairment of beta-cell function. Diabetes. 2008 Jul;57(7):1887-95. doi: 10.2337/db07-1326. Epub 2008 Mar 28. [Article]
  12. Visinoni S, Khalid NF, Joannides CN, Shulkes A, Yim M, Whitehead J, Tiganis T, Lamont BJ, Favaloro JM, Proietto J, Andrikopoulos S, Fam BC: The role of liver fructose-1,6-bisphosphatase in regulating appetite and adiposity. Diabetes. 2012 May;61(5):1122-32. doi: 10.2337/db11-1511. [Article]
  13. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
  14. Zhang Y, Liang JY, Huang S, Ke H, Lipscomb WN: Crystallographic studies of the catalytic mechanism of the neutral form of fructose-1,6-bisphosphatase. Biochemistry. 1993 Feb 23;32(7):1844-57. [Article]
  15. Xue Y, Huang S, Liang JY, Zhang Y, Lipscomb WN: Crystal structure of fructose-1,6-bisphosphatase complexed with fructose 2,6-bisphosphate, AMP, and Zn2+ at 2.0-A resolution: aspects of synergism between inhibitors. Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12482-6. [Article]
  16. Lai C, Gum RJ, Daly M, Fry EH, Hutchins C, Abad-Zapatero C, von Geldern TW: Benzoxazole benzenesulfonamides as allosteric inhibitors of fructose-1,6-bisphosphatase. Bioorg Med Chem Lett. 2006 Apr 1;16(7):1807-10. Epub 2006 Jan 30. [Article]
  17. von Geldern TW, Lai C, Gum RJ, Daly M, Sun C, Fry EH, Abad-Zapatero C: Benzoxazole benzenesulfonamides are novel allosteric inhibitors of fructose-1,6-bisphosphatase with a distinct binding mode. Bioorg Med Chem Lett. 2006 Apr 1;16(7):1811-5. Epub 2006 Jan 25. [Article]
  18. Hebeisen P, Kuhn B, Kohler P, Gubler M, Huber W, Kitas E, Schott B, Benz J, Joseph C, Ruf A: Allosteric FBPase inhibitors gain 10(5) times in potency when simultaneously binding two neighboring AMP sites. Bioorg Med Chem Lett. 2008 Aug 15;18(16):4708-12. doi: 10.1016/j.bmcl.2008.06.103. Epub 2008 Jul 5. [Article]
  19. Kikawa Y, Inuzuka M, Jin BY, Kaji S, Koga J, Yamamoto Y, Fujisawa K, Hata I, Nakai A, Shigematsu Y, Mizunuma H, Taketo A, Mayumi M, Sudo M: Identification of genetic mutations in Japanese patients with fructose-1,6-bisphosphatase deficiency. Am J Hum Genet. 1997 Oct;61(4):852-61. [Article]
  20. Matsuura T, Chinen Y, Arashiro R, Katsuren K, Tamura T, Hyakuna N, Ohta T: Two newly identified genomic mutations in a Japanese female patient with fructose-1,6-bisphosphatase (FBPase) deficiency. Mol Genet Metab. 2002 Jul;76(3):207-10. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB027782,5-Anhydroglucitol-1,6-BiphosphateexperimentalunknownDetails
DB04493Fructose-6-phosphateexperimentalunknownDetails
DB05053MB-07803investigationalunknownDetails
DB00131Adenosine phosphateapproved, investigational, nutraceuticalunknownantagonistinhibitory allosteric modulatorDetails
DB05518Managlinat dialanetilinvestigationalunknownDetails
DB07270N-[7-(3-AMINOPHENYL)-5-METHOXY-1,3-BENZOXAZOL-2-YL]-2,5-DICHLOROBENZENESULFONAMIDEexperimentalunknownDetails
DB073122,5-DICHLORO-N-(5-CHLORO-1,3-BENZOXAZOL-2-YL)BENZENESULFONAMIDEexperimentalunknownDetails
DB073212,5-DICHLORO-N-[5-METHOXY-7-(6-METHOXYPYRIDIN-3-YL)-1,3-BENZOXAZOL-2-YL]BENZENESULFONAMIDEexperimentalunknownDetails
DB04175Mdl-29951experimentalunknownDetails
DB02848{4-[3-(6,7-Diethoxy-Quinazolin-4-Ylamino)-Phenyl]-Thiazol-2-Yl}-MethanolexperimentalunknownDetails
DB084844-AMINO-N-[(2-SULFANYLETHYL)CARBAMOYL]BENZENESULFONAMIDEexperimentalunknownDetails