F262_MOUSE
ID F262_MOUSE Reviewed; 519 AA.
AC P70265; Q8VEI9;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-SEP-2009, sequence version 2.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2;
DE Short=6PF-2-K/Fru-2,6-P2ase 2;
DE Short=PFK/FBPase 2;
DE AltName: Full=6PF-2-K/Fru-2,6-P2ase heart-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=Pfkfb2;
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].
RC STRAIN=BALB/cJ; TISSUE=Kidney;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-469 AND SER-486, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Lung, Spleen, and
RC Testis;
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 -!- 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 -!- TISSUE SPECIFICITY: Highest levels in kidney; also found in heart,
CC brain, spleen, lung, liver, skeletal muscle and testis.
CC -!- PTM: Phosphorylation by AMPK stimulates activity. {ECO:0000250}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the phosphoglycerate
CC mutase family. {ECO:0000305}.
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DR EMBL; X98847; CAA67352.1; -; mRNA.
DR EMBL; BC018418; AAH18418.1; -; mRNA.
DR PIR; S74242; S74242.
DR RefSeq; NP_032851.2; NM_008825.4.
DR AlphaFoldDB; P70265; -.
DR SMR; P70265; -.
DR BioGRID; 202123; 7.
DR ComplexPortal; CPX-2042; 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 complex.
DR IntAct; P70265; 2.
DR STRING; 10090.ENSMUSP00000127587; -.
DR iPTMnet; P70265; -.
DR PhosphoSitePlus; P70265; -.
DR EPD; P70265; -.
DR jPOST; P70265; -.
DR MaxQB; P70265; -.
DR PaxDb; P70265; -.
DR PeptideAtlas; P70265; -.
DR PRIDE; P70265; -.
DR ProteomicsDB; 271836; -.
DR DNASU; 18640; -.
DR GeneID; 18640; -.
DR KEGG; mmu:18640; -.
DR CTD; 5208; -.
DR MGI; MGI:107815; Pfkfb2.
DR eggNOG; KOG0234; Eukaryota.
DR InParanoid; P70265; -.
DR OrthoDB; 392001at2759; -.
DR PhylomeDB; P70265; -.
DR BRENDA; 2.7.1.105; 3474.
DR BRENDA; 3.1.3.46; 3474.
DR Reactome; R-MMU-9634600; Regulation of glycolysis by fructose 2,6-bisphosphate metabolism.
DR BioGRID-ORCS; 18640; 0 hits in 74 CRISPR screens.
DR ChiTaRS; Pfkfb2; mouse.
DR PRO; PR:P70265; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; P70265; protein.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0003873; F:6-phosphofructo-2-kinase activity; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004331; F:fructose-2,6-bisphosphate 2-phosphatase activity; IDA:CACAO.
DR GO; GO:0019900; F:kinase binding; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
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 GO; GO:0006007; P:glucose catabolic process; ISO:MGI.
DR GO; GO:0006096; P:glycolytic process; ISS:UniProtKB.
DR GO; GO:0006089; P:lactate metabolic process; ISO:MGI.
DR GO; GO:0033133; P:positive regulation of glucokinase activity; ISO:MGI.
DR GO; GO:0032024; P:positive regulation of insulin secretion; ISO:MGI.
DR GO; GO:0006090; P:pyruvate metabolic process; ISO:MGI.
DR GO; GO:0009749; P:response to glucose; ISO:MGI.
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; ATP-binding; Hydrolase; Kinase; Multifunctional enzyme;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:O60825"
FT CHAIN 2..519
FT /note="6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase
FT 2"
FT /id="PRO_0000179965"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2..251
FT /note="6-phosphofructo-2-kinase"
FT REGION 252..519
FT /note="Fructose-2,6-bisphosphatase"
FT REGION 448..493
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 500..519
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..21
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 456..484
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 131
FT /evidence="ECO:0000255"
FT ACT_SITE 161
FT /evidence="ECO:0000255"
FT ACT_SITE 260
FT /note="Tele-phosphohistidine intermediate"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT ACT_SITE 329
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 48..56
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 81
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 259
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 266
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 272
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 340
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 351..354
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P07953"
FT BINDING 354
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 358
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 369
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 395..399
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P07953"
FT BINDING 395
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 399
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /evidence="ECO:0000250|UniProtKB:P07953"
FT BINDING 431
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT SITE 259
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT SITE 266
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT SITE 394
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:O60825"
FT MOD_RES 32
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250"
FT MOD_RES 469
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 471
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O60825"
FT MOD_RES 478
FT /note="Phosphothreonine; by PKC"
FT /evidence="ECO:0000250|UniProtKB:P26285"
FT MOD_RES 486
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 496
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O60825"
FT CONFLICT 9
FT /note="T -> P (in Ref. 2; AAH18418)"
FT /evidence="ECO:0000305"
FT CONFLICT 12
FT /note="Missing (in Ref. 2; AAH18418)"
FT /evidence="ECO:0000305"
FT CONFLICT 222
FT /note="M -> I (in Ref. 2; AAH18418)"
FT /evidence="ECO:0000305"
FT CONFLICT 496
FT /note="S -> K (in Ref. 1; CAA67352)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 519 AA; 59925 MW; FD4CF41AEDF22F89 CRC64;
MSENSTFSTE DSCNSSYKPH ASNLRRAGKT CSWASYMTNS PTLIVMIGLP ARGKTYVSKK
LTRYLNWIGV PTKVFNLGVY RREAVKSYQS YDFFRHDNEE AMKIRKQCAL VALEDVKAYF
TEESGQIAVF DATNTTRERR DMILNFAKQN AFKVFFVESV CDDPDVIAAN ILEVKVSSPD
YPERNRENVM EDFLKRIECY KVTYQPLDPD NYDKDLSFIK VMNVGQRFLV NRVQDYIQSK
IVYYLMNIHV HPRTIYLCRH GESEFNLLGK IGGDSGLSVR GKQFAHALKK FLEEQEIQDL
KVWTSQLKRT IQTAESLGVT YEQWKILNEI DAGVCEEMTY SEIEQRYPEE FALRDQEKYL
YRYPGGESYQ DLVQRLEPVI MELERQGNIL VISHQAVMRC LLAYFLDKGA DELPYLRCPL
HIIFKLTPVA YGCKVETITL NVDAVDTHRD KPTHNFPKSQ TPVRMRRNSF TPLSSSNTIR
RPRNYSVGSR PLKPLSPLRA LDMQEGADQP KTQVSIPVV
