ID F16P2_HUMAN Reviewed; 339 AA. AC O00757; Q17R39; Q6FI53; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 27-SEP-2005, sequence version 2. DT 07-JUL-2009, entry version 74. DE RecName: Full=Fructose-1,6-bisphosphatase isozyme 2; DE Short=FBPase 2; DE EC=3.1.3.11; DE AltName: Full=D-fructose-1,6-bisphosphate 1-phosphohydrolase 2; GN Name=FBP2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT LEU-86. RC TISSUE=Skeletal muscle; RX MEDLINE=98339216; PubMed=9678974; DOI=10.1016/S0378-1119(98)00181-4; RA Tillman H., Eschrich K.; RT "Isolation and characterization of an allelic cDNA for human muscle RT fructose-1,6-bisphosphatase."; RL Gene 212:295-304(1998). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., RA Korn B., Zuo D., Hu Y., LaBaer J.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [3] 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., RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R., RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., RA 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., RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., RA 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., RA Rogers J., Dunham I.; RT "DNA sequence and analysis of human chromosome 9."; RL Nature 429:369-374(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LEU-86. RC TISSUE=Colon; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP ENZYME REGULATION, COFACTOR, MUTAGENESIS OF LYS-21; THR-178 AND RP GLN-180, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=16213487; DOI=10.1016/j.febslet.2005.09.021; RA Rakus D., Maciaszczyk E., Wawrzycka D., Ulaszewski S., Eschrich K., RA Dzugaj A.; RT "The origin of the high sensitivity of muscle fructose 1,6- RT bisphosphatase towards AMP."; RL FEBS Lett. 579:5577-5581(2005). RN [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-216, AND MASS RP SPECTROMETRY. RX PubMed=18083107; DOI=10.1016/j.cell.2007.11.025; RA Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., RA Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., RA Mitchell J., Wetzel R., Macneill J., Ren J.M., Yuan J., RA Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., RA Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.; RT "Global survey of phosphotyrosine signaling identifies oncogenic RT kinases in lung cancer."; RL Cell 131:1190-1203(2007). CC -!- CATALYTIC ACTIVITY: D-fructose 1,6-bisphosphate + H(2)O = D- CC fructose 6-phosphate + phosphate. CC -!- COFACTOR: Binds 3 magnesium ions per subunit (By similarity). CC -!- ENZYME 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 CC inhibitor. Fructose-2,6-biphosphate acts as competitive inhibitor. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=1.3 uM for fructose-1,6-biphosphate; CC -!- PATHWAY: Carbohydrate biosynthesis; gluconeogenesis. CC -!- SUBUNIT: Homotetramer (By similarity). CC -!- SIMILARITY: Belongs to the FBPase class 1 family. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; Y10812; CAA71772.1; -; mRNA. DR EMBL; CR536483; CAG38722.1; -; mRNA. DR EMBL; AL161728; CAH72694.1; -; Genomic_DNA. DR EMBL; BC113632; AAI13633.1; -; mRNA. DR EMBL; BC117477; AAI17478.1; -; mRNA. DR IPI; IPI00299456; -. DR RefSeq; NP_003828.2; -. DR UniGene; Hs.61255; -. DR HSSP; P09467; 1FTA. DR SMR; O00757; 9-335. DR IntAct; O00757; 1. DR PhosphoSite; O00757; -. DR PRIDE; O00757; -. DR Ensembl; ENSG00000130957; Homo sapiens. DR GeneID; 8789; -. DR KEGG; hsa:8789; -. DR NMPDR; fig|9606.3.peg.31580; -. DR UCSC; uc004auv.1; human. DR GeneCards; GC09M096360; -. DR H-InvDB; HIX0034872; -. DR HGNC; HGNC:3607; FBP2. DR HPA; HPA012513; -. DR MIM; 603027; gene. DR PharmGKB; PA28019; -. DR HOGENOM; O00757; -. DR HOVERGEN; O00757; -. DR OMA; O00757; ATGELTQ. DR BRENDA; 3.1.3.11; 247. DR Reactome; REACT_474; Metabolism of carbohydrates. DR NextBio; 32964; -. DR ArrayExpress; O00757; -. DR Bgee; O00757; -. DR CleanEx; HS_FBP2; -. DR GermOnline; ENSG00000130957; Homo sapiens. DR GO; GO:0005829; C:cytosol; EXP:Reactome. DR GO; GO:0042132; F:fructose 1,6-bisphosphate 1-phosphatase act...; EXP:Reactome. DR GO; GO:0004331; F:fructose-2,6-bisphosphate 2-phosphatase act...; TAS:ProtInc. DR GO; GO:0000287; F:magnesium ion binding; IEA:UniProtKB-KW. DR GO; GO:0006000; P:fructose metabolic process; TAS:ProtInc. DR GO; GO:0006094; P:gluconeogenesis; IEA:UniProtKB-KW. DR InterPro; IPR000146; Fructose_bisphosphatase. DR InterPro; IPR017955; IMPase/FBPase. DR PANTHER; PTHR11556; In_FB_phphtase; 1. DR Pfam; PF00316; FBPase; 1. DR PRINTS; PR00115; FBPHPHTASE. DR PRINTS; PR00377; INFBPHPHTASE. DR ProDom; PD001491; In_FB_phphtase; 1. DR PROSITE; PS00124; FBPASE; 1. PE 1: Evidence at protein level; KW Allosteric enzyme; Carbohydrate metabolism; Complete proteome; KW Gluconeogenesis; Hydrolase; Magnesium; Metal-binding; Phosphoprotein; KW Polymorphism. FT CHAIN 1 339 Fructose-1,6-bisphosphatase isozyme 2. FT /FTId=PRO_0000200504. FT NP_BIND 18 22 AMP (By similarity). FT NP_BIND 28 32 AMP (By similarity). FT NP_BIND 113 114 AMP (By similarity). FT REGION 122 125 Substrate binding (By similarity). FT REGION 213 216 Substrate binding (By similarity). FT REGION 244 249 Substrate binding (By similarity). FT REGION 275 277 Substrate binding (By similarity). FT METAL 69 69 Magnesium 1 (By similarity). FT METAL 98 98 Magnesium 1 (By similarity). FT METAL 98 98 Magnesium 2 (By similarity). FT METAL 119 119 Magnesium 2 (By similarity). FT METAL 119 119 Magnesium 3 (By similarity). FT METAL 121 121 Magnesium 2; via carbonyl oxygen (By FT similarity). FT METAL 122 122 Magnesium 3 (By similarity). FT METAL 281 281 Magnesium 3 (By similarity). FT BINDING 141 141 AMP (By similarity). FT BINDING 265 265 Substrate (By similarity). FT MOD_RES 216 216 Phosphotyrosine. FT VARIANT 86 86 V -> L (in dbSNP:rs573212). FT /FTId=VAR_024448. FT MUTAGEN 21 21 K->E: Reduces sensitivity to AMP; when FT associated with M-178 and C-180. FT MUTAGEN 178 178 T->M: Reduces sensitivity to AMP; when FT associated with E-21 and C-180. FT MUTAGEN 180 180 Q->C: Reduces sensitivity to AMP; when FT associated with E-21 and M-178. SQ SEQUENCE 339 AA; 36743 MW; 196B06D744710BC4 CRC64; MTDRSPFETD MLTLTRYVME KGRQAKGTGE LTQLLNSMLT AIKAISSAVR KAGLAHLYGI AGSVNVTGDE VKKLDVLSNS LVINMVQSSY STCVLVSEEN KDAIITAKEK RGKYVVCFDP LDGSSNIDCL ASIGTIFAIY RKTSEDEPSE KDALQCGRNI VAAGYALYGS ATLVALSTGQ GVDLFMLDPA LGEFVLVEKD VKIKKKGKIY SLNEGYAKYF DAATTEYVQK KKFPEDGSAP YGARYVGSMV ADVHRTLVYG GIFLYPANQK SPKGKLRLLY ECNPVAYIIE QAGGLATTGT QPVLDVKPEA IHQRVPLILG SPEDVQEYLT CVQKNQAGS //