F261_MOUSE
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 03-AUG-2022, entry version 168.
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}.
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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; P70266; -.
DR PRIDE; P70266; -.
DR ProteomicsDB; 275570; -. [P70266-1]
DR ProteomicsDB; 275571; -. [P70266-2]
DR Antibodypedia; 533; 266 antibodies from 28 providers.
DR DNASU; 18639; -.
DR Ensembl; ENSMUST00000080884; ENSMUSP00000079692; ENSMUSG00000025271. [P70266-2]
DR Ensembl; ENSMUST00000112713; ENSMUSP00000108333; ENSMUSG00000025271. [P70266-1]
DR GeneID; 18639; -.
DR KEGG; mmu:18639; -.
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; RHRTIYL; -.
DR OrthoDB; 392001at2759; -.
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 60 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 177 other tissues.
DR ExpressionAtlas; P70266; baseline and differential.
DR Genevisible; P70266; MM.
DR GO; GO:0043540; C:6-phosphofructo-2-kinase/fructose-2,6-biphosphatase complex; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
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; ISS:UniProtKB.
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:0033133; P:positive regulation of glucokinase activity; 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; 3.40.50.1240; -; 1.
DR Gene3D; 3.40.50.300; -; 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; PTHR10606; 1.
DR Pfam; PF01591; 6PF2K; 1.
DR Pfam; PF00300; His_Phos_1; 1.
DR PRINTS; PR00991; 6PFRUCTKNASE.
DR SMART; SM00855; PGAM; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF53254; SSF53254; 1.
DR PROSITE; PS00175; PG_MUTASE; 1.
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
