F263_RAT
ID F263_RAT Reviewed; 555 AA.
AC O35552; O35096; O35553; O35554; O35555; O35556; O35557; Q9QWQ5; Q9QWQ6;
DT 24-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3;
DE Short=6PF-2-K/Fru-2,6-P2ase 3;
DE Short=PFK/FBPase 3;
DE AltName: Full=6PF-2-K/Fru-2,6-P2ase brain-type isozyme;
DE AltName: Full=RB2K;
DE Includes:
DE RecName: Full=6-phosphofructo-2-kinase;
DE EC=2.7.1.105 {ECO:0000250|UniProtKB:Q16875};
DE Includes:
DE RecName: Full=Fructose-2,6-bisphosphatase;
DE EC=3.1.3.46 {ECO:0000250|UniProtKB:Q16875};
GN Name=Pfkfb3;
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], AND ALTERNATIVE SPLICING.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=9202288; DOI=10.1046/j.1471-4159.1997.69010001.x;
RA Watanabe F., Sakai A., Furuya E.;
RT "Novel isoforms of rat brain fructose 6-phosphate 2-kinase/fructose 2,6-
RT bisphosphatase are generated by tissue-specific alternative splicing.";
RL J. Neurochem. 69:1-9(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 61-369.
RC STRAIN=Wistar; TISSUE=Placenta;
RA Sakakibara R.;
RL Submitted (AUG-1997) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Catalyzes both the synthesis and degradation of fructose 2,6-
CC bisphosphate. {ECO:0000250|UniProtKB:Q16875}.
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:Q16875};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17290;
CC Evidence={ECO:0000250|UniProtKB:Q16875};
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:Q16875};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15654;
CC Evidence={ECO:0000250|UniProtKB:Q16875};
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q16875}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=8;
CC Name=1; Synonyms=RB2K1;
CC IsoId=O35552-1; Sequence=Displayed;
CC Name=2; Synonyms=RB2K2;
CC IsoId=O35552-2; Sequence=VSP_004682;
CC Name=3; Synonyms=RB2K3;
CC IsoId=O35552-3; Sequence=VSP_004683;
CC Name=4; Synonyms=RB2K4;
CC IsoId=O35552-4; Sequence=VSP_004681;
CC Name=5; Synonyms=RB2K5;
CC IsoId=O35552-5; Sequence=VSP_004681, VSP_004682;
CC Name=6; Synonyms=RB2K6;
CC IsoId=O35552-6; Sequence=VSP_004681, VSP_004683;
CC Name=7; Synonyms=RB2K7;
CC IsoId=O35552-7; Sequence=VSP_004684;
CC Name=8; Synonyms=RB2K8;
CC IsoId=O35552-8; Sequence=VSP_004681, VSP_004684;
CC -!- PTM: Phosphorylation by AMPK stimulates activity.
CC {ECO:0000250|UniProtKB:Q16875}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the phosphoglycerate
CC mutase family. {ECO:0000305}.
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DR EMBL; D87240; BAA21749.1; -; mRNA.
DR EMBL; D87241; BAA21750.1; -; mRNA.
DR EMBL; D87242; BAA21751.1; -; mRNA.
DR EMBL; D87243; BAA21752.1; -; mRNA.
DR EMBL; D87244; BAA21753.1; -; mRNA.
DR EMBL; D87245; BAA21754.1; -; mRNA.
DR EMBL; D87246; BAA21755.1; -; mRNA.
DR EMBL; D87247; BAA21756.1; -; mRNA.
DR EMBL; AB006710; BAA22048.1; -; mRNA.
DR RefSeq; NP_476476.1; NM_057135.1. [O35552-1]
DR RefSeq; XP_006254254.1; XM_006254192.3. [O35552-3]
DR RefSeq; XP_006254255.1; XM_006254193.3. [O35552-2]
DR RefSeq; XP_006254258.1; XM_006254196.3. [O35552-4]
DR RefSeq; XP_006254259.1; XM_006254197.3. [O35552-6]
DR RefSeq; XP_006254260.1; XM_006254198.3. [O35552-5]
DR AlphaFoldDB; O35552; -.
DR SMR; O35552; -.
DR ComplexPortal; CPX-2043; 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 complex.
DR IntAct; O35552; 2.
DR STRING; 10116.ENSRNOP00000062965; -.
DR iPTMnet; O35552; -.
DR PhosphoSitePlus; O35552; -.
DR jPOST; O35552; -.
DR PaxDb; O35552; -.
DR Ensembl; ENSRNOT00000025700; ENSRNOP00000025700; ENSRNOG00000018911. [O35552-2]
DR Ensembl; ENSRNOT00000025731; ENSRNOP00000025731; ENSRNOG00000018911. [O35552-4]
DR Ensembl; ENSRNOT00000051067; ENSRNOP00000040928; ENSRNOG00000018911. [O35552-3]
DR Ensembl; ENSRNOT00000068354; ENSRNOP00000062965; ENSRNOG00000018911. [O35552-1]
DR GeneID; 117276; -.
DR KEGG; rno:117276; -.
DR CTD; 5209; -.
DR RGD; 619776; Pfkfb3.
DR eggNOG; KOG0234; Eukaryota.
DR GeneTree; ENSGT00950000182835; -.
DR HOGENOM; CLU_006383_1_1_1; -.
DR InParanoid; O35552; -.
DR OMA; AEDTRIC; -.
DR OrthoDB; 392001at2759; -.
DR PhylomeDB; O35552; -.
DR TreeFam; TF313541; -.
DR BRENDA; 3.1.3.46; 5301.
DR Reactome; R-RNO-9634600; Regulation of glycolysis by fructose 2,6-bisphosphate metabolism.
DR PRO; PR:O35552; -.
DR Proteomes; UP000002494; Chromosome 17.
DR Bgee; ENSRNOG00000018911; Expressed in skeletal muscle tissue and 19 other tissues.
DR ExpressionAtlas; O35552; baseline and differential.
DR Genevisible; O35552; RN.
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; ISS:UniProtKB.
DR GO; GO:0007420; P:brain development; IEP:RGD.
DR GO; GO:0006003; P:fructose 2,6-bisphosphate metabolic process; IDA:RGD.
DR GO; GO:0006000; P:fructose metabolic process; IEA:InterPro.
DR GO; GO:0006110; P:regulation of glycolytic process; TAS: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 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..555
FT /note="6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase
FT 3"
FT /id="PRO_0000179969"
FT REGION 1..245
FT /note="6-phosphofructo-2-kinase"
FT REGION 246..555
FT /note="Fructose-2,6-bisphosphatase"
FT REGION 475..504
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 125
FT /evidence="ECO:0000255"
FT ACT_SITE 155
FT /evidence="ECO:0000255"
FT ACT_SITE 254
FT /note="Tele-phosphohistidine intermediate"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT ACT_SITE 323
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 42..50
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 75
FT /ligand="beta-D-fructose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:57634"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 99
FT /ligand="beta-D-fructose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:57634"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 127
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 164..169
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 169
FT /ligand="beta-D-fructose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:57634"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 190
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 253
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 260
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 334
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 345..348
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P07953"
FT BINDING 348
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 352
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 363
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 389..393
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P07953"
FT BINDING 389
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 393
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /evidence="ECO:0000250|UniProtKB:P07953"
FT BINDING 425
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT SITE 253
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT SITE 260
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT SITE 388
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT MOD_RES 490
FT /note="Phosphoserine; by AMPK and PKA"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT MOD_RES 492
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT MOD_RES 496
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT VAR_SEQ 448..476
FT /note="Missing (in isoform 4, isoform 5, isoform 6 and
FT isoform 8)"
FT /evidence="ECO:0000305"
FT /id="VSP_004681"
FT VAR_SEQ 535..555
FT /note="PLLGKACLRTVCHIFSKFSPY -> NMRSPRSGAESSQKH (in isoform
FT 3 and isoform 6)"
FT /evidence="ECO:0000305"
FT /id="VSP_004683"
FT VAR_SEQ 543..555
FT /note="RTVCHIFSKFSPY -> T (in isoform 2 and isoform 5)"
FT /evidence="ECO:0000305"
FT /id="VSP_004682"
FT VAR_SEQ 543..555
FT /note="Missing (in isoform 7 and isoform 8)"
FT /evidence="ECO:0000305"
FT /id="VSP_004684"
FT CONFLICT 185
FT /note="D -> H (in Ref. 2; BAA22048)"
FT /evidence="ECO:0000305"
FT CONFLICT 367
FT /note="V -> L (in Ref. 2; BAA22048)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 555 AA; 63676 MW; 45B2D090B44FCD8D CRC64;
MPLELTQSRV QKIWVPVDHR PSLPRSCGPK LTNSPTVIVM VGLPARGKTY ISKKLTRYLN
WIGVPTKVFN VGEYRREAVK QYSSYNFFRP DNEEAMRVRK QCALAALRDV KSYLTKEGGQ
IAVFDATNTT RERRHMILHF AKENDFKAFF IESVCDDPTV VASNIMEVKI SSPDYKDCNS
AEAMDDFMKR INCYEASYQP LDPDKCDRDL SFIKVIDVGR RFLVNRVQDH IQSRIVYYLM
NIHVQPRTIY LCRHGENEYN VQGKIGGDSG LSSRGKKFAN ALSKFVEEQN LKDLRVWTSQ
LKSTIQTAEA LRLPYEQWKA LNEIDAGVCE ELTYEEIRDT YPEEYALREQ DKYYYRYPTG
ESYQDLVQRL EPVIMELERQ ENVLVICHQA VLRCLLAYFL DKSAEEMPYL KCPLHTVLKL
TPVAYGCRVE SIYLNVESVS THRERSEAVK IQHFASVVRP SSYTELDFLS VESAKQDAKK
GPNPLMRRNS VTPLASPEPT KKPRINSFEE HVASTSAALP SCLPPEVPTQ LPGQPLLGKA
CLRTVCHIFS KFSPY
