F264_MOUSE
ID F264_MOUSE Reviewed; 469 AA.
AC Q6DTY7; Q5UD55; Q5UD56; Q5UD57; Q5Y296; Q6PFE8;
DT 12-DEC-2006, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4;
DE Short=6PF-2-K/Fru-2,6-P2ase 4;
DE Short=PFK/FBPase 4;
DE AltName: Full=6PF-2-K/Fru-2,6-P2ase testis-type isozyme;
DE Includes:
DE RecName: Full=6-phosphofructo-2-kinase;
DE EC=2.7.1.105;
DE Includes:
DE RecName: Full=Fructose-2,6-bisphosphatase;
DE EC=3.1.3.46;
GN Name=Pfkfb4;
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 [MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Testis;
RX PubMed=14623077; DOI=10.1016/s0014-5793(03)01179-7;
RA Minchenko O.H., Opentanova I.L., Caro J.;
RT "Hypoxic regulation of the 6-phosphofructo-2-kinase/fructose-2,6-
RT bisphosphatase gene family (PFKFB-1-4) expression in vivo.";
RL FEBS Lett. 554:264-270(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6).
RC STRAIN=C57BL/6J; TISSUE=Testis;
RX PubMed=16311927; DOI=10.1007/s11010-005-8009-6;
RA Minchenko O.H., Ogura T., Opentanova I.L., Minchenko D.O., Esumi H.;
RT "Splice isoform of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-4:
RT expression and hypoxic regulation.";
RL Mol. Cell. Biochem. 280:227-234(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3 AND 4).
RC STRAIN=C57BL/6J; TISSUE=Testis;
RA Minchenko D.O., Opentanova I.L., Minchenko O.H.;
RT "Alternative splice isoforms of mouse 6-phosphofructo-2-kinase/fructose-
RT 2,6-biphosphatase 4.";
RL Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=NOD;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
RC STRAIN=C57BL/6J; TISSUE=Brain;
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).
CC -!- FUNCTION: Synthesis and degradation of fructose 2,6-bisphosphate.
CC {ECO:0000250}.
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 -!- 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 -!- ACTIVITY REGULATION: The most important regulatory mechanism of these
CC opposing activities is by phosphorylation and dephosphorylation of the
CC enzyme. {ECO:0000250}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=1;
CC IsoId=Q6DTY7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6DTY7-2; Sequence=VSP_021959;
CC Name=3;
CC IsoId=Q6DTY7-3; Sequence=VSP_021964;
CC Name=4;
CC IsoId=Q6DTY7-4; Sequence=VSP_021962, VSP_021963;
CC Name=5;
CC IsoId=Q6DTY7-5; Sequence=VSP_021961;
CC Name=6;
CC IsoId=Q6DTY7-6; Sequence=VSP_021960;
CC -!- SIMILARITY: In the C-terminal section; belongs to the phosphoglycerate
CC mutase family. {ECO:0000305}.
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DR EMBL; AY646092; AAT72897.2; -; mRNA.
DR EMBL; AY707862; AAU88258.1; -; mRNA.
DR EMBL; DQ350638; ABC71307.1; -; mRNA.
DR EMBL; AY756065; AAV32501.1; -; mRNA.
DR EMBL; AY756066; AAV32502.1; -; mRNA.
DR EMBL; AY756067; AAV32503.1; -; mRNA.
DR EMBL; AK155172; BAE33093.1; -; mRNA.
DR EMBL; BC057594; AAH57594.1; -; mRNA.
DR CCDS; CCDS23541.1; -. [Q6DTY7-1]
DR RefSeq; NP_766607.3; NM_173019.5. [Q6DTY7-1]
DR RefSeq; XP_006512201.1; XM_006512138.2.
DR RefSeq; XP_017168891.1; XM_017313402.1. [Q6DTY7-6]
DR AlphaFoldDB; Q6DTY7; -.
DR SMR; Q6DTY7; -.
DR ComplexPortal; CPX-2046; 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 complex.
DR STRING; 10090.ENSMUSP00000057197; -.
DR iPTMnet; Q6DTY7; -.
DR PhosphoSitePlus; Q6DTY7; -.
DR MaxQB; Q6DTY7; -.
DR PaxDb; Q6DTY7; -.
DR PeptideAtlas; Q6DTY7; -.
DR PRIDE; Q6DTY7; -.
DR ProteomicsDB; 275572; -. [Q6DTY7-1]
DR ProteomicsDB; 275573; -. [Q6DTY7-2]
DR ProteomicsDB; 275574; -. [Q6DTY7-3]
DR ProteomicsDB; 275575; -. [Q6DTY7-4]
DR ProteomicsDB; 275576; -. [Q6DTY7-5]
DR ProteomicsDB; 275577; -. [Q6DTY7-6]
DR Antibodypedia; 30130; 193 antibodies from 24 providers.
DR DNASU; 270198; -.
DR Ensembl; ENSMUST00000051873; ENSMUSP00000057197; ENSMUSG00000025648. [Q6DTY7-5]
DR Ensembl; ENSMUST00000198140; ENSMUSP00000142378; ENSMUSG00000025648. [Q6DTY7-1]
DR Ensembl; ENSMUST00000199591; ENSMUSP00000142992; ENSMUSG00000025648. [Q6DTY7-3]
DR GeneID; 270198; -.
DR KEGG; mmu:270198; -.
DR UCSC; uc009rri.1; mouse. [Q6DTY7-1]
DR UCSC; uc009rrk.1; mouse. [Q6DTY7-5]
DR CTD; 5210; -.
DR MGI; MGI:2687284; Pfkfb4.
DR VEuPathDB; HostDB:ENSMUSG00000025648; -.
DR eggNOG; KOG0234; Eukaryota.
DR GeneTree; ENSGT00950000182835; -.
DR HOGENOM; CLU_006383_1_1_1; -.
DR InParanoid; Q6DTY7; -.
DR OMA; IACMNGR; -.
DR OrthoDB; 392001at2759; -.
DR PhylomeDB; Q6DTY7; -.
DR TreeFam; TF313541; -.
DR Reactome; R-MMU-9634600; Regulation of glycolysis by fructose 2,6-bisphosphate metabolism.
DR BioGRID-ORCS; 270198; 1 hit in 75 CRISPR screens.
DR ChiTaRS; Pfkfb4; mouse.
DR PRO; PR:Q6DTY7; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q6DTY7; protein.
DR Bgee; ENSMUSG00000025648; Expressed in granulocyte and 195 other tissues.
DR ExpressionAtlas; Q6DTY7; baseline and differential.
DR Genevisible; Q6DTY7; MM.
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; IEA:UniProtKB-KW.
DR GO; GO:0004331; F:fructose-2,6-bisphosphate 2-phosphatase activity; IBA:GO_Central.
DR GO; GO:0006003; P:fructose 2,6-bisphosphate metabolic process; IBA:GO_Central.
DR GO; GO:0006000; P:fructose metabolic process; IEA:InterPro.
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 2: Evidence at transcript level;
KW Alternative splicing; ATP-binding; Hydrolase; Kinase;
KW Multifunctional enzyme; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Transferase.
FT CHAIN 1..469
FT /note="6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase
FT 4"
FT /id="PRO_0000268187"
FT REGION 1..249
FT /note="6-phosphofructo-2-kinase"
FT REGION 250..469
FT /note="Fructose-2,6-bisphosphatase"
FT ACT_SITE 129
FT /evidence="ECO:0000255"
FT ACT_SITE 159
FT /evidence="ECO:0000255"
FT ACT_SITE 257
FT /note="Tele-phosphohistidine intermediate"
FT /evidence="ECO:0000250|UniProtKB:P07953"
FT ACT_SITE 326
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:P07953"
FT BINDING 46..54
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 79
FT /ligand="beta-D-fructose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:57634"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 103
FT /ligand="beta-D-fructose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:57634"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 131
FT /ligand="beta-D-fructose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:57634"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 137
FT /ligand="beta-D-fructose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:57634"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 168..173
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 173
FT /ligand="beta-D-fructose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:57634"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 194
FT /ligand="beta-D-fructose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:57634"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 198
FT /ligand="beta-D-fructose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:57634"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 256
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 263
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 269
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /evidence="ECO:0000250|UniProtKB:P07953"
FT BINDING 306
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 337
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /evidence="ECO:0000250|UniProtKB:P07953"
FT BINDING 348..351
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P07953"
FT BINDING 351
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /evidence="ECO:0000250|UniProtKB:P07953"
FT BINDING 355
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /evidence="ECO:0000250|UniProtKB:P07953"
FT BINDING 366
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /evidence="ECO:0000250|UniProtKB:P07953"
FT BINDING 392..396
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P07953"
FT BINDING 392
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /evidence="ECO:0000250|UniProtKB:P07953"
FT BINDING 396
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /evidence="ECO:0000250|UniProtKB:P07953"
FT BINDING 428
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT SITE 391
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:P00950"
FT MOD_RES 29
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000255"
FT MOD_RES 444
FT /note="Phosphothreonine; by PKC"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..218
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_021959"
FT VAR_SEQ 1..34
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:16311927"
FT /id="VSP_021960"
FT VAR_SEQ 33..48
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_021961"
FT VAR_SEQ 212..221
FT /note="DLSYIKIMDV -> SSGQSRRLFS (in isoform 4)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_021962"
FT VAR_SEQ 222..469
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_021963"
FT VAR_SEQ 358..469
FT /note="YRYPKGESYEDLVQRLEPVIMELERQENVLVICHQAVMRCLLAYFLDKAAEE
FT LPYLKCPLHTVLKLTPVAYGCKVESIFLNVAAVNTHRDRPQNVDISRPSEEALVTVPAH
FT Q -> PMKTWCSGWSPSSWNWRGRRMCWSFATRLSCAASWPTSLTRQLKSCPTSNAPCT
FT QS (in isoform 3)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_021964"
SQ SEQUENCE 469 AA; 54067 MW; 53777000F163DDE7 CRC64;
MASPRELTQN PLKKIWMPYS NGRPALHASQ RGVCMTNCPT LIVMVGLPAR GKTYISKKLT
RYLNWIGVPT REFNVGQYRR DIVKTYKSFE FFLPDNEEGL KIRKQCALAA LSDVRKFLSE
EGGHVAVFDA TNTTRERRAM IFNFGEQNGY KTFFVESICV DPEVVAANIV QVKLGSPDYV
NRDSDEATED FMRRIECYEN SYESLDEDLD RDLSYIKIMD VGQSYVVNRV ADHIQSRIVY
YLMNIHVTPR SIYLCRHGES ELNLKGRIGG DPGLSPRGRE FSKHLAQFIS DQNIKDLKVW
TSQMKRTIQT AEALSVPYEQ WKVLNEIDAG VCEEMTYEEI QDHYPLEFAL RDQDKYRYRY
PKGESYEDLV QRLEPVIMEL ERQENVLVIC HQAVMRCLLA YFLDKAAEEL PYLKCPLHTV
LKLTPVAYGC KVESIFLNVA AVNTHRDRPQ NVDISRPSEE ALVTVPAHQ
