F263_PONAB
ID F263_PONAB Reviewed; 514 AA.
AC Q5R9C1; Q5R404; Q5R5L4;
DT 22-JUL-2008, integrated into UniProtKB/Swiss-Prot.
DT 22-JUL-2008, sequence version 2.
DT 03-AUG-2022, entry version 77.
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/placenta-type isozyme;
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 Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Brain cortex, and Kidney;
RG The German cDNA consortium;
RL Submitted (NOV-2004) 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=3;
CC Name=1;
CC IsoId=Q5R9C1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5R9C1-2; Sequence=VSP_034919, VSP_034920;
CC Name=3;
CC IsoId=Q5R9C1-3; Sequence=VSP_034919, VSP_034921;
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; CR859468; CAH91639.1; -; mRNA.
DR EMBL; CR860843; CAH92952.1; -; mRNA.
DR EMBL; CR861456; CAH93512.1; -; mRNA.
DR RefSeq; NP_001125963.1; NM_001132491.1.
DR RefSeq; NP_001128959.1; NM_001135487.1.
DR AlphaFoldDB; Q5R9C1; -.
DR SMR; Q5R9C1; -.
DR STRING; 9601.ENSPPYP00000002394; -.
DR PRIDE; Q5R9C1; -.
DR Ensembl; ENSPPYT00000039436; ENSPPYP00000035295; ENSPPYG00000002068. [Q5R9C1-1]
DR Ensembl; ENSPPYT00000044028; ENSPPYP00000028360; ENSPPYG00000002068. [Q5R9C1-3]
DR GeneID; 100172898; -.
DR KEGG; pon:100172898; -.
DR CTD; 5209; -.
DR eggNOG; KOG0234; Eukaryota.
DR GeneTree; ENSGT00950000182835; -.
DR InParanoid; Q5R9C1; -.
DR Proteomes; UP000001595; Chromosome 10.
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:0006003; P:fructose 2,6-bisphosphate metabolic process; IEA:InterPro.
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..514
FT /note="6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase
FT 3"
FT /id="PRO_0000345149"
FT REGION 1..245
FT /note="6-phosphofructo-2-kinase"
FT REGION 246..514
FT /note="Fructose-2,6-bisphosphatase"
FT REGION 444..475
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 461
FT /note="Phosphoserine; by AMPK and PKA"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT MOD_RES 463
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT MOD_RES 467
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT MOD_RES 471
FT /note="Phosphothreonine; by PKC"
FT /evidence="ECO:0000250"
FT VAR_SEQ 3..26
FT /note="LELTQSRVQKIWVPVDHRPSLPRS -> FRKA (in isoform 2 and
FT isoform 3)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_034919"
FT VAR_SEQ 506..514
FT /note="PLLGQACLT -> NMKGSRSSADSSRKH (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_034920"
FT VAR_SEQ 514
FT /note="T -> RTVCHIFSKFSPY (in isoform 3)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_034921"
FT CONFLICT 37
FT /note="V -> A (in Ref. 1; CAH92952)"
FT /evidence="ECO:0000305"
FT CONFLICT 224
FT /note="V -> A (in Ref. 1; CAH93512)"
FT /evidence="ECO:0000305"
FT CONFLICT 326
FT /note="A -> V (in Ref. 1; CAH91639)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 514 AA; 58876 MW; 18FD1D267306853D CRC64;
MPLELTQSRV QKIWVPVDHR PSLPRSCGPK LTNSPTVIVM VGLPARGKTY ISKKLTRYLN
WIGVPTKVFN VGEYRREAVK QYSSYNFFRP DNEEAMKVRK QCALAALRDV KSYLAKEGGQ
IAVFDATNTT RERRHMILHF AKENDFKAFF IESVCDDPTV VASNIMEVKI SSPDYKDCNS
AEAMDDFMKR ISCYEASYQP LDPDKCDRDL SLIKVIDVGR RFLVNRVQDH IQSRIVYYLM
NIHVQPRTIY LCRHGENEHN LQGRIGGDSG LSSRGKKFAS ALSKFVEEQN LKDLRVWTSQ
LKSTIQTAEA LRLPYEQWKA LNEIDAGVCE ELTYEEIRDT YPEEYALREQ DKYYYRYPTG
ESYQDLVQRL EPVIMELERQ ENVLVICHQA VLRCLLAYFL DKSAEEMPYL KCPLHTVLKL
TPVAYGCRVE SIYLNVESVC THRERSEDAK KGPNPLMRRN SVTPLASPEP TKKPRINSFE
EHVASTSAAL PSCLPPEVPT QLPGQPLLGQ ACLT
