ID F261_MOUSE Reviewed; 471 AA. AC P70266; A2AFN0; Q3V180; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 09-JAN-2007, sequence version 2. DT 27-MAR-2024, entry version 177. DE RecName: Full=6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 1 {ECO:0000305}; DE Short=6PF-2-K/Fru-2,6-P2ase 1; DE Short=PFK/FBPase 1; DE AltName: Full=6PF-2-K/Fru-2,6-P2ase liver isozyme; DE Includes: DE RecName: Full=6-phosphofructo-2-kinase; DE EC=2.7.1.105 {ECO:0000250|UniProtKB:P07953}; DE Includes: DE RecName: Full=Fructose-2,6-bisphosphatase; DE EC=3.1.3.46 {ECO:0000250|UniProtKB:P07953}; GN Name=Pfkfb1 {ECO:0000312|MGI:MGI:107816}; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC STRAIN=C57BL/6J; TISSUE=Head; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] OF 402-471 (ISOFORM 1). RC STRAIN=BALB/cJ; TISSUE=Liver; RX PubMed=8814283; DOI=10.1016/0014-5793(96)00878-2; RA Batra R.S., Brown R.M., Brown G.K., Craig I.W.; RT "Molecular cloning and tissue-specific expression of mouse kidney 6- RT phosphofructo-2-kinase/fructose-2,6-bisphosphatase."; RL FEBS Lett. 393:167-173(1996). RN [4] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brown adipose tissue, and Liver; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). CC -!- FUNCTION: Synthesis and degradation of fructose 2,6-bisphosphate. CC {ECO:0000250|UniProtKB:P07953}. CC -!- CATALYTIC ACTIVITY: CC Reaction=beta-D-fructose 2,6-bisphosphate + H2O = beta-D-fructose 6- CC phosphate + phosphate; Xref=Rhea:RHEA:17289, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:57634, ChEBI:CHEBI:58579; EC=3.1.3.46; CC Evidence={ECO:0000250|UniProtKB:P07953}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17290; CC Evidence={ECO:0000250|UniProtKB:P07953}; CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + beta-D-fructose 6-phosphate = ADP + beta-D-fructose 2,6- CC bisphosphate + H(+); Xref=Rhea:RHEA:15653, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:57634, ChEBI:CHEBI:58579, CC ChEBI:CHEBI:456216; EC=2.7.1.105; CC Evidence={ECO:0000250|UniProtKB:P07953}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15654; CC Evidence={ECO:0000250|UniProtKB:P07953}; CC -!- ACTIVITY REGULATION: Phosphorylation at Ser-33 inhibits the kinase and CC activates the bisphosphatase. {ECO:0000250|UniProtKB:P07953}. CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P07953}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P70266-1; Sequence=Displayed; CC Name=2; CC IsoId=P70266-2; Sequence=VSP_022168; CC -!- TISSUE SPECIFICITY: Liver. CC -!- SIMILARITY: In the C-terminal section; belongs to the phosphoglycerate CC mutase family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AK132629; BAE21271.1; -; mRNA. DR EMBL; AL672150; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; X98848; CAA67353.1; -; mRNA. DR CCDS; CCDS30464.1; -. [P70266-2] DR CCDS; CCDS90763.1; -. [P70266-1] DR PIR; S74243; S74243. DR RefSeq; NP_032850.1; NM_008824.3. [P70266-2] DR RefSeq; XP_006528818.1; XM_006528755.2. DR RefSeq; XP_011246093.1; XM_011247791.2. DR AlphaFoldDB; P70266; -. DR BMRB; P70266; -. DR SMR; P70266; -. DR ComplexPortal; CPX-2039; 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 1 complex. DR STRING; 10090.ENSMUSP00000079692; -. DR iPTMnet; P70266; -. DR PhosphoSitePlus; P70266; -. DR EPD; P70266; -. DR jPOST; P70266; -. DR MaxQB; P70266; -. DR PaxDb; 10090-ENSMUSP00000079692; -. DR ProteomicsDB; 275570; -. [P70266-1] DR ProteomicsDB; 275571; -. [P70266-2] DR Antibodypedia; 533; 288 antibodies from 28 providers. DR DNASU; 18639; -. DR Ensembl; ENSMUST00000080884.11; ENSMUSP00000079692.5; ENSMUSG00000025271.14. [P70266-2] DR Ensembl; ENSMUST00000112713.3; ENSMUSP00000108333.3; ENSMUSG00000025271.14. [P70266-1] DR GeneID; 18639; -. DR KEGG; mmu:18639; -. DR AGR; MGI:107816; -. DR CTD; 5207; -. DR MGI; MGI:107816; Pfkfb1. DR VEuPathDB; HostDB:ENSMUSG00000025271; -. DR eggNOG; KOG0234; Eukaryota. DR GeneTree; ENSGT00950000182835; -. DR HOGENOM; CLU_006383_1_1_1; -. DR InParanoid; P70266; -. DR OMA; GECYGMT; -. DR OrthoDB; 2013830at2759; -. DR PhylomeDB; P70266; -. DR TreeFam; TF313541; -. DR Reactome; R-MMU-9634600; Regulation of glycolysis by fructose 2,6-bisphosphate metabolism. DR BioGRID-ORCS; 18639; 1 hit in 63 CRISPR screens. DR ChiTaRS; Pfkfb1; mouse. DR PRO; PR:P70266; -. DR Proteomes; UP000000589; Chromosome X. DR RNAct; P70266; Protein. DR Bgee; ENSMUSG00000025271; Expressed in hindlimb stylopod muscle and 180 other cell types or tissues. DR ExpressionAtlas; P70266; baseline and differential. DR GO; GO:0043540; C:6-phosphofructo-2-kinase/fructose-2,6-biphosphatase complex; ISS:UniProtKB. DR GO; GO:0005829; C:cytosol; ISO:MGI. DR GO; GO:0003873; F:6-phosphofructo-2-kinase activity; ISO:MGI. DR GO; GO:0005524; F:ATP binding; ISO:MGI. DR GO; GO:0004331; F:fructose-2,6-bisphosphate 2-phosphatase activity; IGI:MGI. DR GO; GO:0070095; F:fructose-6-phosphate binding; ISO:MGI. DR GO; GO:0042802; F:identical protein binding; ISO:MGI. DR GO; GO:0019900; F:kinase binding; ISO:MGI. DR GO; GO:0031100; P:animal organ regeneration; IEA:Ensembl. DR GO; GO:0046835; P:carbohydrate phosphorylation; ISO:MGI. DR GO; GO:0006003; P:fructose 2,6-bisphosphate metabolic process; ISS:UniProtKB. DR GO; GO:0006000; P:fructose metabolic process; IEA:InterPro. DR GO; GO:1904539; P:negative regulation of glycolytic process through fructose-6-phosphate; IMP:MGI. DR GO; GO:0045722; P:positive regulation of gluconeogenesis; ISO:MGI. DR GO; GO:1904540; P:positive regulation of glycolytic process through fructose-6-phosphate; ISO:MGI. DR GO; GO:0051591; P:response to cAMP; IEA:Ensembl. DR GO; GO:0033762; P:response to glucagon; IEA:Ensembl. DR GO; GO:0051384; P:response to glucocorticoid; IEA:Ensembl. DR GO; GO:0032868; P:response to insulin; IEA:Ensembl. DR GO; GO:0042594; P:response to starvation; IEA:Ensembl. DR CDD; cd07067; HP_PGM_like; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR Gene3D; 3.40.50.1240; Phosphoglycerate mutase-like; 1. DR InterPro; IPR003094; 6Pfruct_kin. DR InterPro; IPR013079; 6Phosfructo_kin. DR InterPro; IPR013078; His_Pase_superF_clade-1. DR InterPro; IPR029033; His_PPase_superfam. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR001345; PG/BPGM_mutase_AS. DR PANTHER; PTHR10606; 6-PHOSPHOFRUCTO-2-KINASE/FRUCTOSE-2,6-BISPHOSPHATASE; 1. DR PANTHER; PTHR10606:SF15; 6-PHOSPHOFRUCTO-2-KINASE_FRUCTOSE-2,6-BISPHOSPHATASE 1; 1. DR Pfam; PF01591; 6PF2K; 1. DR Pfam; PF00300; His_Phos_1; 1. DR PIRSF; PIRSF000709; 6PFK_2-Ptase; 1. DR PRINTS; PR00991; 6PFRUCTKNASE. DR SMART; SM00855; PGAM; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR SUPFAM; SSF53254; Phosphoglycerate mutase-like; 1. DR PROSITE; PS00175; PG_MUTASE; 1. DR Genevisible; P70266; MM. PE 1: Evidence at protein level; KW Acetylation; Alternative splicing; ATP-binding; Hydrolase; Kinase; KW Multifunctional enzyme; Nucleotide-binding; Phosphoprotein; KW Reference proteome; Transferase. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000250|UniProtKB:P07953" FT CHAIN 2..471 FT /note="6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase FT 1" FT /id="PRO_0000179961" FT REGION 2..250 FT /note="6-phosphofructo-2-kinase" FT /evidence="ECO:0000250" FT REGION 251..471 FT /note="Fructose-2,6-bisphosphatase" FT /evidence="ECO:0000250" FT ACT_SITE 131 FT /evidence="ECO:0000255" FT ACT_SITE 161 FT /evidence="ECO:0000255" FT ACT_SITE 259 FT /note="Tele-phosphohistidine intermediate" FT /evidence="ECO:0000250|UniProtKB:P07953" FT ACT_SITE 328 FT /note="Proton donor/acceptor" FT /evidence="ECO:0000250|UniProtKB:P07953" FT BINDING 49..57 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:Q16875" FT BINDING 82 FT /ligand="beta-D-fructose 6-phosphate" FT /ligand_id="ChEBI:CHEBI:57634" FT /evidence="ECO:0000250|UniProtKB:Q16875" FT BINDING 105 FT /ligand="beta-D-fructose 6-phosphate" FT /ligand_id="ChEBI:CHEBI:57634" FT /evidence="ECO:0000250|UniProtKB:Q16875" FT BINDING 133 FT /ligand="beta-D-fructose 6-phosphate" FT /ligand_id="ChEBI:CHEBI:57634" FT /evidence="ECO:0000250|UniProtKB:Q16875" FT BINDING 139 FT /ligand="beta-D-fructose 6-phosphate" FT /ligand_id="ChEBI:CHEBI:57634" FT /evidence="ECO:0000250|UniProtKB:Q16875" FT BINDING 170..175 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:Q16875" FT BINDING 175 FT /ligand="beta-D-fructose 6-phosphate" FT /ligand_id="ChEBI:CHEBI:57634" FT /evidence="ECO:0000250|UniProtKB:Q16875" FT BINDING 196 FT /ligand="beta-D-fructose 6-phosphate" FT /ligand_id="ChEBI:CHEBI:57634" FT /evidence="ECO:0000250|UniProtKB:Q16875" FT BINDING 200 FT /ligand="beta-D-fructose 6-phosphate" FT /ligand_id="ChEBI:CHEBI:57634" FT /evidence="ECO:0000250|UniProtKB:Q16875" FT BINDING 258 FT /ligand="beta-D-fructose 2,6-bisphosphate" FT /ligand_id="ChEBI:CHEBI:58579" FT /evidence="ECO:0000250|UniProtKB:Q16875" FT BINDING 265 FT /ligand="beta-D-fructose 2,6-bisphosphate" FT /ligand_id="ChEBI:CHEBI:58579" FT /evidence="ECO:0000250|UniProtKB:Q16875" FT BINDING 271 FT /ligand="beta-D-fructose 2,6-bisphosphate" FT /ligand_id="ChEBI:CHEBI:58579" FT /evidence="ECO:0000250|UniProtKB:P07953" FT BINDING 308 FT /ligand="beta-D-fructose 2,6-bisphosphate" FT /ligand_id="ChEBI:CHEBI:58579" FT /evidence="ECO:0000250|UniProtKB:Q16875" FT BINDING 339 FT /ligand="beta-D-fructose 2,6-bisphosphate" FT /ligand_id="ChEBI:CHEBI:58579" FT /evidence="ECO:0000250|UniProtKB:P07953" FT BINDING 350..353 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P07953" FT BINDING 353 FT /ligand="beta-D-fructose 2,6-bisphosphate" FT /ligand_id="ChEBI:CHEBI:58579" FT /evidence="ECO:0000250|UniProtKB:P07953" FT BINDING 357 FT /ligand="beta-D-fructose 2,6-bisphosphate" FT /ligand_id="ChEBI:CHEBI:58579" FT /evidence="ECO:0000250|UniProtKB:P07953" FT BINDING 368 FT /ligand="beta-D-fructose 2,6-bisphosphate" FT /ligand_id="ChEBI:CHEBI:58579" FT /evidence="ECO:0000250|UniProtKB:P07953" FT BINDING 394..398 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P07953" FT BINDING 394 FT /ligand="beta-D-fructose 2,6-bisphosphate" FT /ligand_id="ChEBI:CHEBI:58579" FT /evidence="ECO:0000250|UniProtKB:P07953" FT BINDING 398 FT /ligand="beta-D-fructose 2,6-bisphosphate" FT /ligand_id="ChEBI:CHEBI:58579" FT /evidence="ECO:0000250|UniProtKB:P07953" FT BINDING 430 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:Q16875" FT SITE 393 FT /note="Transition state stabilizer" FT /evidence="ECO:0000250|UniProtKB:P00950" FT MOD_RES 2 FT /note="N-acetylserine" FT /evidence="ECO:0000250|UniProtKB:P07953" FT MOD_RES 33 FT /note="Phosphoserine; by PKA" FT /evidence="ECO:0000250|UniProtKB:P07953" FT MOD_RES 141 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P07953" FT VAR_SEQ 1..33 FT /note="MSREMGELTQTRLQKIWIPHSSSSSLLQRRRGS -> MEEKASKRAA (in FT isoform 2)" FT /evidence="ECO:0000303|PubMed:16141072" FT /id="VSP_022168" FT CONFLICT 460 FT /note="P -> A (in Ref. 3; CAA67353)" FT /evidence="ECO:0000305" SQ SEQUENCE 471 AA; 54849 MW; A8EA464FB4B2DA42 CRC64; MSREMGELTQ TRLQKIWIPH SSSSSLLQRR RGSSIPQFTN SPTMVIMVGL PARGKTYIST KLTRYLNWIG TPTKVFNLGQ YRREAVSYRN YEFFRPDNME AQLIRKQCAL AALKDVHKYL SREEGHVAVF DATNTTRERR SLILQFAKEH GYKVFFIESI CNDPDIIAEN IKQVKLGSPD YIDCDQEKVL EDFLKRIECY EINYQPLDEE LDSHLSYIKI FDVGTRYMVN RVQDHVQSRT AYYLMNIHVT PRSIYLCRHG ESELNLRGRI GGDSGLSARG KQYAYALANF IRSQSISSLK VWTSHMKRTI QTAEALGVPY EQWKALNEID AGVCEEMTYE EIQEHYPEEF ALRDQDKYRY RYPKGESYED LVQRLEPVIM ELERQENVLV ICHQAVMRCL LAYFLDKSSD ELPYLKCPLH TVLKLTPVAY GCRVESIYLN VEAVNTHRDK PENVDITREP EEALDTVPAH Y //