F16P1_HUMAN
ID F16P1_HUMAN Reviewed; 338 AA.
AC P09467; O75571; Q53F94; Q96E46;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 02-NOV-2010, sequence version 5.
DT 03-AUG-2022, entry version 224.
DE RecName: Full=Fructose-1,6-bisphosphatase 1;
DE Short=FBPase 1;
DE EC=3.1.3.11 {ECO:0000269|PubMed:17350621, ECO:0000269|PubMed:8387495};
DE AltName: Full=D-fructose-1,6-bisphosphate 1-phosphohydrolase 1;
DE AltName: Full=Liver FBPase;
GN Name=FBP1; Synonyms=FBP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT LYS-218.
RX PubMed=2842796; DOI=10.1073/pnas.85.18.6904;
RA Solomon D.H., Raynal M.-C., Tejwani G.A., Cayre Y.E.;
RT "Activation of the fructose 1,6-bisphosphatase gene by 1,25-
RT dihydroxyvitamin D3 during monocytic differentiation.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:6904-6908(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 2-11, CATALYTIC ACTIVITY,
RP MUTAGENESIS OF ASP-119 AND ASP-122, AND VARIANT LYS-218.
RC TISSUE=Liver;
RX PubMed=8387495; DOI=10.1016/s0021-9258(18)98373-0;
RA El-Maghrabi M.R., Gidh-Jain M., Austin L.R., Pilkis S.J.;
RT "Isolation of a human liver fructose-1,6-bisphosphatase cDNA and expression
RT of the protein in Escherichia coli. Role of Asp-118 and Asp-121 in
RT catalysis.";
RL J. Biol. Chem. 268:9466-9472(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT LYS-218.
RC TISSUE=Kidney, Liver, and Monocyte;
RX PubMed=8135811; DOI=10.1006/bbrc.1994.1283;
RA Kikawa Y., Inuzuka M., Takano T., Shigematsu Y., Nakai A., Yamamoto Y.,
RA Jin B.Y., Koga J., Taketo A., Sudo M.;
RT "cDNA sequences encoding human fructose 1,6-bisphosphatase from monocytes,
RT liver and kidney: application of monocytes to molecular analysis of human
RT fructose 1,6-bisphosphatase deficiency.";
RL Biochem. Biophys. Res. Commun. 199:687-693(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT LYS-218.
RC TISSUE=Liver;
RX PubMed=7558035; DOI=10.1006/geno.1995.1085;
RA El-Maghrabi M.R., Lang A.J., Jiang W., Yamagata K., Stoffel M., Takeda J.,
RA Fernald A.A., le Beau M.M., Bell G.I., Baker L., Pilkis S.J.;
RT "Human fructose-1,6-bisphosphatase gene (FBP1): exon-intron organization,
RT localization to chromosome bands 9q22.2-q22.3, and mutation screening in
RT subjects with fructose-1,6-bisphosphatase deficiency.";
RL Genomics 27:520-525(1995).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION, AND VARIANT LYS-218.
RC TISSUE=Lung;
RX PubMed=10222032; DOI=10.1006/abbi.1999.1120;
RA Skalecki K., Rakus D., Wisniewski J.R., Kolodziej J., Dzugaj A.;
RT "cDNA sequence and kinetic properties of human lung fructose(1,
RT 6)bisphosphatase.";
RL Arch. Biochem. Biophys. 365:1-9(1999).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LYS-218.
RC TISSUE=Thymus;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS LYS-218; ILE-233 AND
RP LEU-255.
RG NIEHS SNPs program;
RL Submitted (DEC-2004) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Urinary bladder;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 320-338.
RC TISSUE=Liver;
RX PubMed=7589895; DOI=10.1046/j.1432-0436.1995.5910051.x;
RA Bertolotti R., Armbruster-Hilbert L., Okayama H.;
RT "Liver fructose-1,6-bisphosphatase cDNA: trans-complementation of fission
RT yeast and characterization of two human transcripts.";
RL Differentiation 59:51-60(1995).
RN [11]
RP FUNCTION.
RX PubMed=16497803; DOI=10.1210/en.2005-1498;
RA Lamont B.J., Visinoni S., Fam B.C., Kebede M., Weinrich B.,
RA Papapostolou S., Massinet H., Proietto J., Favaloro J., Andrikopoulos S.;
RT "Expression of human fructose-1,6-bisphosphatase in the liver of transgenic
RT mice results in increased glycerol gluconeogenesis.";
RL Endocrinology 147:2764-2772(2006).
RN [12]
RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP MUTAGENESIS OF GLN-70.
RX PubMed=17350621; DOI=10.1016/j.febslet.2007.02.051;
RA Zarzycki M., Maciaszczyk E., Dzugaj A.;
RT "Glu 69 is essential for the high sensitivity of muscle fructose-1,6-
RT bisphosphatase inhibition by calcium ions.";
RL FEBS Lett. 581:1347-1350(2007).
RN [13]
RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=18375435; DOI=10.2337/db07-1326;
RA Kebede M., Favaloro J., Gunton J.E., Laybutt D.R., Shaw M., Wong N.,
RA Fam B.C., Aston-Mourney K., Rantzau C., Zulli A., Proietto J.,
RA Andrikopoulos S.;
RT "Fructose-1,6-bisphosphatase overexpression in pancreatic beta-cells
RT results in reduced insulin secretion: a new mechanism for fat-induced
RT impairment of beta-cell function.";
RL Diabetes 57:1887-1895(2008).
RN [14]
RP FUNCTION.
RX PubMed=22517657; DOI=10.2337/db11-1511;
RA Visinoni S., Khalid N.F., Joannides C.N., Shulkes A., Yim M., Whitehead J.,
RA Tiganis T., Lamont B.J., Favaloro J.M., Proietto J., Andrikopoulos S.,
RA Fam B.C.;
RT "The role of liver fructose-1,6-bisphosphatase in regulating appetite and
RT adiposity.";
RL Diabetes 61:1122-1132(2012).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-265, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEXES WITH MAGNESIUM IONS AND
RP SUBSTRATE ANALOGS, AND COFACTOR.
RX PubMed=8382525; DOI=10.1021/bi00058a019;
RA Zhang Y., Liang J.-Y., Huang S., Ke H., Lipscomb W.N.;
RT "Crystallographic studies of the catalytic mechanism of the neutral form of
RT fructose-1,6-bisphosphatase.";
RL Biochemistry 32:1844-1857(1993).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH
RP FRUCTOSE-2,6-BISPHOSPHATE; AMP AND ZINC, SUBUNIT, COFACTOR, AND ACTIVITY
RP REGULATION.
RX PubMed=7809062; DOI=10.1073/pnas.91.26.12482;
RA Xue Y., Huang S., Liang J.-Y., Zhang Y., Lipscomb W.N.;
RT "Crystal structure of fructose-1,6-bisphosphatase complexed with fructose
RT 2,6-bisphosphate, AMP, and Zn2+ at 2.0-A resolution: aspects of synergism
RT between inhibitors.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:12482-12486(1994).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.81 ANGSTROMS) IN COMPLEX WITH BENZOXAZOLE
RP BENZENESULFONAMIDES, SUBUNIT, AND ACTIVITY REGULATION.
RX PubMed=16446092; DOI=10.1016/j.bmcl.2006.01.014;
RA Lai C., Gum R.J., Daly M., Fry E.H., Hutchins C., Abad-Zapatero C.,
RA von Geldern T.W.;
RT "Benzoxazole benzenesulfonamides as allosteric inhibitors of fructose-1,6-
RT bisphosphatase.";
RL Bioorg. Med. Chem. Lett. 16:1807-1810(2006).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.95 ANGSTROMS) IN COMPLEX WITH BENZOXAZOLE
RP BENZENESULFONAMIDES, SUBUNIT, AND ACTIVITY REGULATION.
RX PubMed=16442285; DOI=10.1016/j.bmcl.2006.01.015;
RA von Geldern T.W., Lai C., Gum R.J., Daly M., Sun C., Fry E.H.,
RA Abad-Zapatero C.;
RT "Benzoxazole benzenesulfonamides are novel allosteric inhibitors of
RT fructose-1,6-bisphosphatase with a distinct binding mode.";
RL Bioorg. Med. Chem. Lett. 16:1811-1815(2006).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEX WITH AROMATIC SULFONYLUREA
RP AMP ANALOGS, SUBUNIT, AND ACTIVITY REGULATION.
RX PubMed=18650089; DOI=10.1016/j.bmcl.2008.06.103;
RA Hebeisen P., Kuhn B., Kohler P., Gubler M., Huber W., Kitas E., Schott B.,
RA Benz J., Joseph C., Ruf A.;
RT "Allosteric FBPase inhibitors gain 10(5) times in potency when
RT simultaneously binding two neighboring AMP sites.";
RL Bioorg. Med. Chem. Lett. 18:4708-4712(2008).
RN [21]
RP VARIANTS FBP1D SER-164 AND ASP-177, AND VARIANT ALA-325.
RX PubMed=9382095; DOI=10.1086/514875;
RA Kikawa Y., Inuzuka M., Jin B.Y., Kaji S., Koga J., Yamamoto Y.,
RA Fujisawa K., Hata I., Nakai A., Shigematsu Y., Mizunuma H., Taketo A.,
RA Mayumi M., Sudo M.;
RT "Identification of genetic mutations in Japanese patients with fructose-
RT 1,6-bisphosphatase deficiency.";
RL Am. J. Hum. Genet. 61:852-861(1997).
RN [22]
RP VARIANTS FBP1D SER-194 AND ARG-284.
RX PubMed=12126934; DOI=10.1016/s1096-7192(02)00038-0;
RA Matsuura T., Chinen Y., Arashiro R., Katsuren K., Tamura T., Hyakuna N.,
RA Ohta T.;
RT "Two newly identified genomic mutations in a Japanese female patient with
RT fructose-1,6-bisphosphatase (FBPase) deficiency.";
RL Mol. Genet. Metab. 76:207-210(2002).
RN [23]
RP VARIANT FBP1D TRP-158.
RX PubMed=25601412; DOI=10.1007/s10545-014-9804-6;
RA Lebigot E., Brassier A., Zater M., Imanci D., Feillet F., Therond P.,
RA de Lonlay P., Boutron A.;
RT "Fructose 1,6-bisphosphatase deficiency: clinical, biochemical and genetic
RT features in French patients.";
RL J. Inherit. Metab. Dis. 38:881-887(2015).
CC -!- FUNCTION: Catalyzes the hydrolysis of fructose 1,6-bisphosphate to
CC fructose 6-phosphate in the presence of divalent cations, acting as a
CC rate-limiting enzyme in gluconeogenesis. Plays a role in regulating
CC glucose sensing and insulin secretion of pancreatic beta-cells. Appears
CC to modulate glycerol gluconeogenesis in liver. Important regulator of
CC appetite and adiposity; increased expression of the protein in liver
CC after nutrient excess increases circulating satiety hormones and
CC reduces appetite-stimulating neuropeptides and thus seems to provide a
CC feedback mechanism to limit weight gain. {ECO:0000269|PubMed:16497803,
CC ECO:0000269|PubMed:18375435, ECO:0000269|PubMed:22517657}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=beta-D-fructose 1,6-bisphosphate + H2O = beta-D-fructose 6-
CC phosphate + phosphate; Xref=Rhea:RHEA:11064, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:32966, ChEBI:CHEBI:43474, ChEBI:CHEBI:57634; EC=3.1.3.11;
CC Evidence={ECO:0000269|PubMed:17350621, ECO:0000269|PubMed:8387495};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:7809062};
CC Note=Binds 3 Mg(2+) ions per subunit. {ECO:0000250|UniProtKB:P00636};
CC -!- ACTIVITY REGULATION: Subject to complex allosteric regulation. The
CC enzyme can assume an active R-state, or an inactive T-state.
CC Intermediate conformations may exist. AMP acts as allosteric inhibitor.
CC AMP binding affects the turnover of bound substrate and not the
CC affinity for substrate. Fructose 2,6-bisphosphate acts as competitive
CC inhibitor. Fructose 2,6-bisphosphate and AMP have synergistic effects.
CC {ECO:0000269|PubMed:16442285, ECO:0000269|PubMed:16446092,
CC ECO:0000269|PubMed:17350621, ECO:0000269|PubMed:18650089,
CC ECO:0000269|PubMed:7809062}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.7 uM for fructose 1,6-biphosphate {ECO:0000269|PubMed:17350621};
CC Note=The kinetic constants are determined for the recombinant enzyme
CC expressed in E.coli.;
CC -!- PATHWAY: Carbohydrate biosynthesis; gluconeogenesis.
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:16442285,
CC ECO:0000269|PubMed:16446092, ECO:0000269|PubMed:18650089,
CC ECO:0000269|PubMed:7809062}.
CC -!- INTERACTION:
CC P09467; O00499: BIN1; NbExp=4; IntAct=EBI-712740, EBI-719094;
CC P09467; Q99814: EPAS1; NbExp=4; IntAct=EBI-712740, EBI-447470;
CC P09467; P09467: FBP1; NbExp=15; IntAct=EBI-712740, EBI-712740;
CC P09467; O00757: FBP2; NbExp=16; IntAct=EBI-712740, EBI-719781;
CC P09467; P51116: FXR2; NbExp=3; IntAct=EBI-712740, EBI-740459;
CC P09467; Q16665: HIF1A; NbExp=5; IntAct=EBI-712740, EBI-447269;
CC P09467; P42858: HTT; NbExp=3; IntAct=EBI-712740, EBI-466029;
CC -!- TISSUE SPECIFICITY: Expressed in pancreatic islets.
CC {ECO:0000269|PubMed:18375435}.
CC -!- INDUCTION: Up-regulated in pancreatic islets of individuals with type 2
CC diabetes. {ECO:0000269|PubMed:18375435}.
CC -!- DISEASE: Fructose-1,6-bisphosphatase deficiency (FBP1D) [MIM:229700]:
CC An autosomal recessive metabolic disorder characterized by impaired
CC gluconeogenesis, and episodes of hypoglycemia and metabolic acidosis
CC that can be lethal in newborn infants or young children.
CC {ECO:0000269|PubMed:12126934, ECO:0000269|PubMed:25601412,
CC ECO:0000269|PubMed:9382095}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the FBPase class 1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC50207.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/fbp1/";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Fructose bisphosphatase entry;
CC URL="https://en.wikipedia.org/wiki/Fructose_bisphosphatase";
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DR EMBL; M19922; AAA35517.1; -; mRNA.
DR EMBL; L10320; AAA35817.1; -; mRNA.
DR EMBL; D26054; BAA05051.1; -; mRNA.
DR EMBL; D26055; BAA05052.1; -; mRNA.
DR EMBL; D26056; BAA05053.1; -; mRNA.
DR EMBL; U21931; AAC50207.1; ALT_SEQ; Genomic_DNA.
DR EMBL; U21925; AAC50207.1; JOINED; Genomic_DNA.
DR EMBL; U21926; AAC50207.1; JOINED; Genomic_DNA.
DR EMBL; U21927; AAC50207.1; JOINED; Genomic_DNA.
DR EMBL; U21929; AAC50207.1; JOINED; Genomic_DNA.
DR EMBL; U21930; AAC50207.1; JOINED; Genomic_DNA.
DR EMBL; AF073475; AAC25774.1; -; mRNA.
DR EMBL; AK223395; BAD97115.1; -; mRNA.
DR EMBL; AY866483; AAW34363.1; -; Genomic_DNA.
DR EMBL; AL161728; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC012927; AAH12927.1; -; mRNA.
DR EMBL; U47919; AAA89098.1; -; mRNA.
DR EMBL; U47918; AAA89097.1; -; mRNA.
DR CCDS; CCDS6712.1; -.
DR PIR; A46666; A46666.
DR RefSeq; NP_000498.2; NM_000507.3.
DR RefSeq; NP_001121100.1; NM_001127628.1.
DR PDB; 1FTA; X-ray; 2.30 A; A/B/C/D=2-338.
DR PDB; 2FHY; X-ray; 2.95 A; A/D/H/L=1-338.
DR PDB; 2FIE; X-ray; 2.81 A; A/D/H/L=1-338.
DR PDB; 2FIX; X-ray; 3.50 A; A/D/H/L=1-338.
DR PDB; 2JJK; X-ray; 2.00 A; A/B/C/D=1-338.
DR PDB; 2VT5; X-ray; 2.20 A; A/B/C/D/E/F/G/H=1-338.
DR PDB; 2WBB; X-ray; 2.22 A; A/B/C/D/E/F/G/H=1-338.
DR PDB; 2WBD; X-ray; 2.40 A; A/B/C/D/E/F/G/H=1-338.
DR PDB; 2Y5K; X-ray; 2.10 A; A/B/C/D=1-338.
DR PDB; 2Y5L; X-ray; 2.20 A; A/B/C/D/E/F/G/H=1-338.
DR PDB; 3A29; X-ray; 2.60 A; A/B/C/D=2-338.
DR PDB; 3KBZ; X-ray; 2.45 A; A/B/C/D=2-338.
DR PDB; 3KC0; X-ray; 2.80 A; A/B/C/D=2-338.
DR PDB; 3KC1; X-ray; 2.25 A; A/B/C/D=2-338.
DR PDB; 4MJO; X-ray; 2.40 A; A/B/C/D/E/F/G/H=1-338.
DR PDB; 5LDZ; X-ray; 2.20 A; A/B/C/D/E/F=1-338.
DR PDB; 5PZQ; X-ray; 2.70 A; A/B/C/D=1-338.
DR PDB; 5PZR; X-ray; 1.90 A; A/B/C/D=1-338.
DR PDB; 5PZS; X-ray; 2.37 A; A/B/C/D=1-338.
DR PDB; 5PZT; X-ray; 2.80 A; A/B/C/D/E/F/G/H=1-338.
DR PDB; 5PZU; X-ray; 1.90 A; A/B/C/D=1-338.
DR PDB; 5PZV; X-ray; 2.00 A; A/B/C/D=1-338.
DR PDB; 5PZW; X-ray; 2.00 A; A/B/C/D=1-338.
DR PDB; 5PZX; X-ray; 2.75 A; A/B/C/D/E/F/G/H=1-338.
DR PDB; 5PZY; X-ray; 2.21 A; A/B/C/D/E/F/G/H=1-338.
DR PDB; 5PZZ; X-ray; 2.50 A; A/B/C/D/E/F/G/H=1-338.
DR PDB; 5Q00; X-ray; 2.60 A; A/B/C/D/E/F/G/H=1-338.
DR PDB; 5Q01; X-ray; 2.60 A; A/B/C/D/E/F/G/H=1-338.
DR PDB; 5Q02; X-ray; 2.10 A; A/B/C/D=1-338.
DR PDB; 5Q03; X-ray; 2.31 A; A/B/C/D/E/F/G/H=1-338.
DR PDB; 5Q04; X-ray; 2.50 A; A/B/C/D/E/F/G/H=1-338.
DR PDB; 5Q05; X-ray; 2.20 A; A/B/C/D/E/F/G/H=1-338.
DR PDB; 5Q06; X-ray; 2.40 A; A/B/C/D=1-338.
DR PDB; 5Q07; X-ray; 2.42 A; A/B/C/D/E/F/G/H=1-338.
DR PDB; 5Q08; X-ray; 2.20 A; A/B/C/D/E/F/G/H=1-338.
DR PDB; 5Q09; X-ray; 1.90 A; A/B/C/D/E/F/G/H=1-338.
DR PDB; 5Q0A; X-ray; 2.30 A; A/B/C/D=1-338.
DR PDB; 5Q0B; X-ray; 2.30 A; A/B/C/D=1-338.
DR PDB; 6LS5; X-ray; 2.03 A; A/B/C/D=1-338.
DR PDB; 6LW2; X-ray; 2.40 A; A/B/C/D=1-338.
DR PDB; 7C9Q; X-ray; 1.88 A; A/B/C/D=1-338.
DR PDB; 7CVH; X-ray; 2.09 A; A/B/C/D=1-338.
DR PDB; 7CVN; X-ray; 2.75 A; A/B/C/D=1-338.
DR PDB; 7CWE; X-ray; 3.00 A; A/B=1-338.
DR PDBsum; 1FTA; -.
DR PDBsum; 2FHY; -.
DR PDBsum; 2FIE; -.
DR PDBsum; 2FIX; -.
DR PDBsum; 2JJK; -.
DR PDBsum; 2VT5; -.
DR PDBsum; 2WBB; -.
DR PDBsum; 2WBD; -.
DR PDBsum; 2Y5K; -.
DR PDBsum; 2Y5L; -.
DR PDBsum; 3A29; -.
DR PDBsum; 3KBZ; -.
DR PDBsum; 3KC0; -.
DR PDBsum; 3KC1; -.
DR PDBsum; 4MJO; -.
DR PDBsum; 5LDZ; -.
DR PDBsum; 5PZQ; -.
DR PDBsum; 5PZR; -.
DR PDBsum; 5PZS; -.
DR PDBsum; 5PZT; -.
DR PDBsum; 5PZU; -.
DR PDBsum; 5PZV; -.
DR PDBsum; 5PZW; -.
DR PDBsum; 5PZX; -.
DR PDBsum; 5PZY; -.
DR PDBsum; 5PZZ; -.
DR PDBsum; 5Q00; -.
DR PDBsum; 5Q01; -.
DR PDBsum; 5Q02; -.
DR PDBsum; 5Q03; -.
DR PDBsum; 5Q04; -.
DR PDBsum; 5Q05; -.
DR PDBsum; 5Q06; -.
DR PDBsum; 5Q07; -.
DR PDBsum; 5Q08; -.
DR PDBsum; 5Q09; -.
DR PDBsum; 5Q0A; -.
DR PDBsum; 5Q0B; -.
DR PDBsum; 6LS5; -.
DR PDBsum; 6LW2; -.
DR PDBsum; 7C9Q; -.
DR PDBsum; 7CVH; -.
DR PDBsum; 7CVN; -.
DR PDBsum; 7CWE; -.
DR AlphaFoldDB; P09467; -.
DR SMR; P09467; -.
DR BioGRID; 108497; 346.
DR DIP; DIP-46677N; -.
DR IntAct; P09467; 49.
DR MINT; P09467; -.
DR STRING; 9606.ENSP00000408025; -.
DR BindingDB; P09467; -.
DR ChEMBL; CHEMBL3975; -.
DR DrugBank; DB02778; 2,5-Anhydroglucitol-1,6-Biphosphate.
DR DrugBank; DB07312; 2,5-DICHLORO-N-(5-CHLORO-1,3-BENZOXAZOL-2-YL)BENZENESULFONAMIDE.
DR DrugBank; DB07321; 2,5-DICHLORO-N-[5-METHOXY-7-(6-METHOXYPYRIDIN-3-YL)-1,3-BENZOXAZOL-2-YL]BENZENESULFONAMIDE.
DR DrugBank; DB08484; 4-AMINO-N-[(2-SULFANYLETHYL)CARBAMOYL]BENZENESULFONAMIDE.
DR DrugBank; DB00131; Adenosine phosphate.
DR DrugBank; DB04493; Fructose-6-phosphate.
DR DrugBank; DB05518; Managlinat dialanetil.
DR DrugBank; DB05053; MB-07803.
DR DrugBank; DB04175; Mdl-29951.
DR DrugBank; DB07270; N-[7-(3-AMINOPHENYL)-5-METHOXY-1,3-BENZOXAZOL-2-YL]-2,5-DICHLOROBENZENESULFONAMIDE.
DR DrugBank; DB02848; {4-[3-(6,7-Diethoxy-Quinazolin-4-Ylamino)-Phenyl]-Thiazol-2-Yl}-Methanol.
DR DrugCentral; P09467; -.
DR MoonProt; P09467; -.
DR DEPOD; FBP1; -.
DR GlyGen; P09467; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P09467; -.
DR PhosphoSitePlus; P09467; -.
DR BioMuta; FBP1; -.
DR DMDM; 311033495; -.
DR CPTAC; CPTAC-200; -.
DR CPTAC; CPTAC-201; -.
DR EPD; P09467; -.
DR jPOST; P09467; -.
DR MassIVE; P09467; -.
DR MaxQB; P09467; -.
DR PaxDb; P09467; -.
DR PeptideAtlas; P09467; -.
DR PRIDE; P09467; -.
DR ProteomicsDB; 52223; -.
DR Antibodypedia; 1620; 291 antibodies from 33 providers.
DR DNASU; 2203; -.
DR Ensembl; ENST00000375326.9; ENSP00000364475.5; ENSG00000165140.12.
DR Ensembl; ENST00000415431.5; ENSP00000408025.1; ENSG00000165140.12.
DR GeneID; 2203; -.
DR KEGG; hsa:2203; -.
DR MANE-Select; ENST00000375326.9; ENSP00000364475.5; NM_000507.4; NP_000498.2.
DR UCSC; uc004auw.5; human.
DR CTD; 2203; -.
DR DisGeNET; 2203; -.
DR GeneCards; FBP1; -.
DR GeneReviews; FBP1; -.
DR HGNC; HGNC:3606; FBP1.
DR HPA; ENSG00000165140; Tissue enhanced (intestine, kidney, liver).
DR MalaCards; FBP1; -.
DR MIM; 229700; phenotype.
DR MIM; 611570; gene.
DR neXtProt; NX_P09467; -.
DR OpenTargets; ENSG00000165140; -.
DR Orphanet; 348; Fructose-1,6-bisphosphatase deficiency.
DR PharmGKB; PA28018; -.
DR VEuPathDB; HostDB:ENSG00000165140; -.
DR eggNOG; KOG1458; Eukaryota.
DR GeneTree; ENSGT00390000015513; -.
DR HOGENOM; CLU_039977_1_0_1; -.
DR InParanoid; P09467; -.
DR OMA; NSRFWEP; -.
DR OrthoDB; 1381522at2759; -.
DR PhylomeDB; P09467; -.
DR TreeFam; TF314824; -.
DR BioCyc; MetaCyc:HS09189-MON; -.
DR BRENDA; 3.1.3.11; 2681.
DR PathwayCommons; P09467; -.
DR Reactome; R-HSA-70263; Gluconeogenesis.
DR SABIO-RK; P09467; -.
DR SignaLink; P09467; -.
DR SIGNOR; P09467; -.
DR UniPathway; UPA00138; -.
DR BioGRID-ORCS; 2203; 24 hits in 1079 CRISPR screens.
DR ChiTaRS; FBP1; human.
DR EvolutionaryTrace; P09467; -.
DR GenomeRNAi; 2203; -.
DR Pharos; P09467; Tchem.
DR PRO; PR:P09467; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; P09467; protein.
DR Bgee; ENSG00000165140; Expressed in right lobe of liver and 128 other tissues.
DR ExpressionAtlas; P09467; baseline and differential.
DR Genevisible; P09467; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IMP:CAFA.
DR GO; GO:0016208; F:AMP binding; IDA:UniProtKB.
DR GO; GO:0042132; F:fructose 1,6-bisphosphate 1-phosphatase activity; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IMP:UniProtKB.
DR GO; GO:0048029; F:monosaccharide binding; ISS:UniProtKB.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IMP:CAFA.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IEA:Ensembl.
DR GO; GO:0071286; P:cellular response to magnesium ion; IDA:UniProtKB.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IDA:UniProtKB.
DR GO; GO:0016311; P:dephosphorylation; IDA:UniProtKB.
DR GO; GO:0030388; P:fructose 1,6-bisphosphate metabolic process; IBA:GO_Central.
DR GO; GO:0006002; P:fructose 6-phosphate metabolic process; IDA:UniProtKB.
DR GO; GO:0006000; P:fructose metabolic process; IBA:GO_Central.
DR GO; GO:0006094; P:gluconeogenesis; IMP:UniProtKB.
DR GO; GO:0030308; P:negative regulation of cell growth; IDA:UniProtKB.
DR GO; GO:0045820; P:negative regulation of glycolytic process; IDA:UniProtKB.
DR GO; GO:0046580; P:negative regulation of Ras protein signal transduction; IDA:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:CAFA.
DR GO; GO:0006111; P:regulation of gluconeogenesis; IMP:UniProtKB.
DR GO; GO:0005986; P:sucrose biosynthetic process; IBA:GO_Central.
DR CDD; cd00354; FBPase; 1.
DR HAMAP; MF_01855; FBPase_class1; 1.
DR InterPro; IPR044015; FBPase_C_dom.
DR InterPro; IPR000146; FBPase_class-1.
DR InterPro; IPR033391; FBPase_N.
DR InterPro; IPR028343; FBPtase.
DR InterPro; IPR020548; Fructose_bisphosphatase_AS.
DR PANTHER; PTHR11556; PTHR11556; 1.
DR Pfam; PF00316; FBPase; 1.
DR Pfam; PF18913; FBPase_C; 1.
DR PIRSF; PIRSF500210; FBPtase; 1.
DR PIRSF; PIRSF000904; FBPtase_SBPase; 1.
DR PRINTS; PR00115; F16BPHPHTASE.
DR PROSITE; PS00124; FBPASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Allosteric enzyme; Carbohydrate metabolism;
KW Direct protein sequencing; Disease variant; Gluconeogenesis; Hydrolase;
KW Magnesium; Metal-binding; Phosphoprotein; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P00637,
FT ECO:0000269|PubMed:8387495"
FT CHAIN 2..338
FT /note="Fructose-1,6-bisphosphatase 1"
FT /id="PRO_0000200498"
FT BINDING 18..22
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000269|PubMed:7809062,
FT ECO:0007744|PDB:1FTA"
FT BINDING 28..32
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000269|PubMed:7809062,
FT ECO:0007744|PDB:1FTA"
FT BINDING 69
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P00636"
FT BINDING 98
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P00636"
FT BINDING 98
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P00636"
FT BINDING 113..114
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000269|PubMed:7809062,
FT ECO:0007744|PDB:1FTA"
FT BINDING 119
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P00636"
FT BINDING 119
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0007744|PDB:2FHY"
FT BINDING 121
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P00636"
FT BINDING 122..125
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P00636"
FT BINDING 122
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0007744|PDB:2FHY"
FT BINDING 141
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000269|PubMed:7809062,
FT ECO:0007744|PDB:1FTA"
FT BINDING 213..216
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P00636"
FT BINDING 244..249
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P00636"
FT BINDING 265
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P00636"
FT BINDING 275..277
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P00636"
FT BINDING 281
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0007744|PDB:2FHY"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:P00637"
FT MOD_RES 151
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9QXD6"
FT MOD_RES 216
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9QXD6"
FT MOD_RES 245
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9QXD6"
FT MOD_RES 265
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VARIANT 158
FT /note="R -> W (in FBP1D; unknown pathological significance;
FT dbSNP:rs766005419)"
FT /evidence="ECO:0000269|PubMed:25601412"
FT /id="VAR_075492"
FT VARIANT 164
FT /note="G -> S (in FBP1D; dbSNP:rs121918188)"
FT /evidence="ECO:0000269|PubMed:9382095"
FT /id="VAR_002380"
FT VARIANT 177
FT /note="A -> D (in FBP1D; dbSNP:rs121918189)"
FT /evidence="ECO:0000269|PubMed:9382095"
FT /id="VAR_002381"
FT VARIANT 194
FT /note="F -> S (in FBP1D; dbSNP:rs121918191)"
FT /evidence="ECO:0000269|PubMed:12126934"
FT /id="VAR_038812"
FT VARIANT 218
FT /note="R -> K (in dbSNP:rs1769259)"
FT /evidence="ECO:0000269|PubMed:10222032,
FT ECO:0000269|PubMed:2842796, ECO:0000269|PubMed:7558035,
FT ECO:0000269|PubMed:8135811, ECO:0000269|PubMed:8387495,
FT ECO:0000269|Ref.6, ECO:0000269|Ref.7"
FT /id="VAR_022212"
FT VARIANT 233
FT /note="F -> I (in dbSNP:rs2297085)"
FT /evidence="ECO:0000269|Ref.7"
FT /id="VAR_022213"
FT VARIANT 255
FT /note="R -> L (in dbSNP:rs28369761)"
FT /evidence="ECO:0000269|Ref.7"
FT /id="VAR_022214"
FT VARIANT 284
FT /note="P -> R (in FBP1D; dbSNP:rs121918192)"
FT /evidence="ECO:0000269|PubMed:12126934"
FT /id="VAR_038813"
FT VARIANT 325
FT /note="V -> A"
FT /evidence="ECO:0000269|PubMed:9382095"
FT /id="VAR_002382"
FT MUTAGEN 70
FT /note="Q->E: Increased affinity towards Ca(2+) and Mg(2+)."
FT /evidence="ECO:0000269|PubMed:17350621"
FT MUTAGEN 119
FT /note="D->A: Reduced activity."
FT /evidence="ECO:0000269|PubMed:8387495"
FT MUTAGEN 122
FT /note="D->A: Reduced activity."
FT /evidence="ECO:0000269|PubMed:8387495"
FT CONFLICT 215
FT /note="G -> A (in Ref. 2; AAA35817 and 5; AAC25774)"
FT /evidence="ECO:0000305"
FT CONFLICT 337
FT /note="A -> G (in Ref. 5; AAC25774)"
FT /evidence="ECO:0000305"
FT HELIX 14..24
FT /evidence="ECO:0007829|PDB:7C9Q"
FT HELIX 30..49
FT /evidence="ECO:0007829|PDB:7C9Q"
FT TURN 50..53
FT /evidence="ECO:0007829|PDB:7C9Q"
FT HELIX 54..57
FT /evidence="ECO:0007829|PDB:7C9Q"
FT TURN 59..61
FT /evidence="ECO:0007829|PDB:7C9Q"
FT HELIX 70..87
FT /evidence="ECO:0007829|PDB:7C9Q"
FT TURN 88..90
FT /evidence="ECO:0007829|PDB:7C9Q"
FT STRAND 92..97
FT /evidence="ECO:0007829|PDB:7C9Q"
FT STRAND 100..102
FT /evidence="ECO:0007829|PDB:7CWE"
FT HELIX 108..110
FT /evidence="ECO:0007829|PDB:7C9Q"
FT STRAND 111..119
FT /evidence="ECO:0007829|PDB:7C9Q"
FT HELIX 124..126
FT /evidence="ECO:0007829|PDB:7CVH"
FT TURN 127..131
FT /evidence="ECO:0007829|PDB:7C9Q"
FT STRAND 133..141
FT /evidence="ECO:0007829|PDB:7C9Q"
FT STRAND 145..147
FT /evidence="ECO:0007829|PDB:5PZW"
FT HELIX 150..153
FT /evidence="ECO:0007829|PDB:7C9Q"
FT HELIX 157..159
FT /evidence="ECO:0007829|PDB:7C9Q"
FT STRAND 161..178
FT /evidence="ECO:0007829|PDB:7C9Q"
FT STRAND 181..187
FT /evidence="ECO:0007829|PDB:7C9Q"
FT TURN 189..191
FT /evidence="ECO:0007829|PDB:7C9Q"
FT STRAND 194..198
FT /evidence="ECO:0007829|PDB:7C9Q"
FT STRAND 208..211
FT /evidence="ECO:0007829|PDB:7C9Q"
FT HELIX 214..219
FT /evidence="ECO:0007829|PDB:7C9Q"
FT HELIX 222..232
FT /evidence="ECO:0007829|PDB:7C9Q"
FT STRAND 235..237
FT /evidence="ECO:0007829|PDB:7CVH"
FT HELIX 249..259
FT /evidence="ECO:0007829|PDB:7C9Q"
FT STRAND 262..265
FT /evidence="ECO:0007829|PDB:7C9Q"
FT STRAND 269..271
FT /evidence="ECO:0007829|PDB:7C9Q"
FT STRAND 275..277
FT /evidence="ECO:0007829|PDB:7C9Q"
FT TURN 278..281
FT /evidence="ECO:0007829|PDB:7C9Q"
FT HELIX 282..291
FT /evidence="ECO:0007829|PDB:7C9Q"
FT STRAND 295..297
FT /evidence="ECO:0007829|PDB:7C9Q"
FT STRAND 299..302
FT /evidence="ECO:0007829|PDB:7C9Q"
FT HELIX 303..305
FT /evidence="ECO:0007829|PDB:7C9Q"
FT STRAND 317..320
FT /evidence="ECO:0007829|PDB:7C9Q"
FT HELIX 322..334
FT /evidence="ECO:0007829|PDB:7C9Q"
SQ SEQUENCE 338 AA; 36842 MW; B3D270BCBB358B71 CRC64;
MADQAPFDTD VNTLTRFVME EGRKARGTGE LTQLLNSLCT AVKAISSAVR KAGIAHLYGI
AGSTNVTGDQ VKKLDVLSND LVMNMLKSSF ATCVLVSEED KHAIIVEPEK RGKYVVCFDP
LDGSSNIDCL VSVGTIFGIY RKKSTDEPSE KDALQPGRNL VAAGYALYGS ATMLVLAMDC
GVNCFMLDPA IGEFILVDKD VKIKKKGKIY SLNEGYARDF DPAVTEYIQR KKFPPDNSAP
YGARYVGSMV ADVHRTLVYG GIFLYPANKK SPNGKLRLLY ECNPMAYVME KAGGMATTGK
EAVLDVIPTD IHQRAPVILG SPDDVLEFLK VYEKHSAQ
