F262_RAT
ID F262_RAT Reviewed; 557 AA.
AC Q9JJH5; Q64297; Q9JHL5; Q9JJH4;
DT 24-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 166.
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 AltName: Full=RH2K;
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=8292038; DOI=10.1006/bbrc.1994.1047;
RA Watanabe F., Sakai A., Furuya E., Uyeda K.;
RT "Molecular cloning and tissue specific expression of fructose 6-
RT phosphate,2-kinase:fructose 2,6-bisphosphatase of rat brain.";
RL Biochem. Biophys. Res. Commun. 198:335-340(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND ALTERNATIVE SPLICING.
RC STRAIN=Sprague-Dawley;
RA Watanabe F., Furuya E.;
RT "New isoforms of rat heart-type fructose 6-phosphate 2-kinase/fructose 2,6-
RT bisphosphatase are generated by alternative splicing of novel exons.";
RL Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-469 AND SER-486, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=3;
CC IsoId=Q9JJH5-1; Sequence=Displayed;
CC Name=1;
CC IsoId=Q9JJH5-2; Sequence=VSP_004677, VSP_004679;
CC Name=2;
CC IsoId=Q9JJH5-3; Sequence=VSP_004676;
CC Name=4;
CC IsoId=Q9JJH5-4; Sequence=VSP_004678;
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; S67900; AAB29678.1; -; mRNA.
DR EMBL; L27084; AAA41132.1; -; mRNA.
DR EMBL; AB040530; BAA96495.1; -; mRNA.
DR EMBL; AB040531; BAA96496.1; -; mRNA.
DR EMBL; AB040532; BAA96497.1; -; mRNA.
DR EMBL; AB040533; BAA96498.1; -; mRNA.
DR PIR; JC2037; JC2037.
DR RefSeq; NP_001029136.1; NM_001033964.2. [Q9JJH5-3]
DR RefSeq; NP_001029137.1; NM_001033965.2. [Q9JJH5-1]
DR RefSeq; NP_536725.2; NM_080477.3. [Q9JJH5-4]
DR RefSeq; XP_006249768.1; XM_006249706.3.
DR RefSeq; XP_006249769.1; XM_006249707.3.
DR RefSeq; XP_006249770.1; XM_006249708.1.
DR RefSeq; XP_006249771.1; XM_006249709.3. [Q9JJH5-4]
DR RefSeq; XP_006249773.1; XM_006249711.3. [Q9JJH5-1]
DR AlphaFoldDB; Q9JJH5; -.
DR SMR; Q9JJH5; -.
DR ComplexPortal; CPX-2041; 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 complex.
DR STRING; 10116.ENSRNOP00000005729; -.
DR iPTMnet; Q9JJH5; -.
DR PhosphoSitePlus; Q9JJH5; -.
DR jPOST; Q9JJH5; -.
DR PaxDb; Q9JJH5; -.
DR Ensembl; ENSRNOT00000005729; ENSRNOP00000005729; ENSRNOG00000004162. [Q9JJH5-1]
DR Ensembl; ENSRNOT00000037679; ENSRNOP00000030819; ENSRNOG00000004162. [Q9JJH5-4]
DR Ensembl; ENSRNOT00000117528; ENSRNOP00000082431; ENSRNOG00000004162. [Q9JJH5-3]
DR GeneID; 24640; -.
DR KEGG; rno:24640; -.
DR UCSC; RGD:3309; rat. [Q9JJH5-1]
DR CTD; 5208; -.
DR RGD; 3309; Pfkfb2.
DR eggNOG; KOG0234; Eukaryota.
DR GeneTree; ENSGT00950000182835; -.
DR HOGENOM; CLU_006383_1_1_1; -.
DR InParanoid; Q9JJH5; -.
DR OMA; KIQARYC; -.
DR OrthoDB; 392001at2759; -.
DR PhylomeDB; Q9JJH5; -.
DR TreeFam; TF313541; -.
DR BRENDA; 2.7.1.105; 5301.
DR BRENDA; 3.1.3.46; 5301.
DR Reactome; R-RNO-9634600; Regulation of glycolysis by fructose 2,6-bisphosphate metabolism.
DR SABIO-RK; Q9JJH5; -.
DR PRO; PR:Q9JJH5; -.
DR Proteomes; UP000002494; Chromosome 13.
DR Bgee; ENSRNOG00000004162; Expressed in stomach and 19 other tissues.
DR ExpressionAtlas; Q9JJH5; baseline and differential.
DR Genevisible; Q9JJH5; RN.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
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; IPI:RGD.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
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; IDA:RGD.
DR GO; GO:0006096; P:glycolytic process; ISS:UniProtKB.
DR GO; GO:0006089; P:lactate metabolic process; IDA:RGD.
DR GO; GO:0033133; P:positive regulation of glucokinase activity; IDA:RGD.
DR GO; GO:0032024; P:positive regulation of insulin secretion; IDA:RGD.
DR GO; GO:0006090; P:pyruvate metabolic process; IDA:RGD.
DR GO; GO:0009749; P:response to glucose; IDA:RGD.
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:O60825"
FT CHAIN 2..557
FT /note="6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase
FT 2"
FT /id="PRO_0000179966"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2..251
FT /note="6-phosphofructo-2-kinase"
FT REGION 252..557
FT /note="Fructose-2,6-bisphosphatase"
FT REGION 449..495
FT /note="Disordered"
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:22673903"
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:22673903"
FT MOD_RES 496
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O60825"
FT VAR_SEQ 454..536
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_004678"
FT VAR_SEQ 514..536
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_004676"
FT VAR_SEQ 515..519
FT /note="QQGSA -> SIPVV (in isoform 1)"
FT /evidence="ECO:0000305"
FT /id="VSP_004677"
FT VAR_SEQ 520..547
FT /note="Missing (in isoform 1)"
FT /evidence="ECO:0000305"
FT /id="VSP_004679"
SQ SEQUENCE 557 AA; 64156 MW; D5707054E416629F CRC64;
MSENSTFSTE DSSSSSYKPH ASNLRRAGKK CSWASYMTNS PTLIVMIGLP ARGKTYVSKK
LTRYLNWIGV PTKVFNLGVY RREAVKSYKS YDFFRHDNEE AMKIRKQCAL VALEDVKAYF
TEESGQIAVF DATNTTRERR DMILNFAKQN AFKVFFVESV CDDPDVIAAN ILEVKVSSPD
YPERNRENVM EDFLKRIECY KVTYQPLDPD NYDKDLSFIK VMNVGQRFLV NRVQDYIQSK
IVYYLMNIHV HPRTIYLCRH GESEFNLLGK IGGDSGLSLR GKQFAQALKK FLEEQEIQDL
KVWTSQLKRT IQTAESLGVT YEQWKILNEI DAGVCEEMTY SEIEQRYPEE FALRDQEKYL
YRYPGGESYQ DLVQRLEPVI MELERQGNVL VISHQAVMRC LLAYFLDKGA DELPYLRCPL
HIIFKLTPVA YGCKVETITL NVEAVDTHRD KPTHNFPKSQ TPVRMRRNSF TPLSSSNTIR
RPRNYSVGSR PLKPLSPLRA LDMQEGADQP KTQVQQGSAQ ATEHLQKALE FANGHREVEN
VLAKHRRPSM ASLTLLS
