F262_BOVIN
ID F262_BOVIN Reviewed; 531 AA.
AC P26285;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 163.
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 Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Heart;
RX PubMed=2164212; DOI=10.1073/pnas.87.13.4951;
RA Sakata J., Uyeda K.;
RT "Bovine heart fructose-6-phosphate 2-kinase/fructose-2,6-bisphosphatase:
RT complete amino acid sequence and localization of phosphorylation sites.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:4951-4955(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Heart;
RX PubMed=8179334; DOI=10.1006/abbi.1994.1194;
RA Tsuchiya Y., Uyeda K.;
RT "Bovine heart fructose 6-P,2-kinase:fructose 2,6-bisphosphatase mRNA and
RT gene structure.";
RL Arch. Biochem. Biophys. 310:467-474(1994).
RN [3]
RP PROTEIN SEQUENCE OF 464-480, AND PHOSPHORYLATION AT SER-467 AND THR-476.
RC TISSUE=Heart;
RX PubMed=2846551; DOI=10.1016/s0021-9258(18)37461-1;
RA Kitamura K., Kangawa K., Matsuo H., Uyeda K.;
RT "Phosphorylation of myocardial fructose-6-phosphate,2-kinase: fructose-2,6-
RT bisphosphatase by cAMP-dependent protein kinase and protein kinase C.
RT Activation by phosphorylation and amino acid sequences of the
RT phosphorylation sites.";
RL J. Biol. Chem. 263:16796-16801(1988).
RN [4]
RP PROTEIN SEQUENCE OF 104-112; 189-204 AND 416-432.
RX PubMed=2539378; DOI=10.1016/s0021-9258(18)83354-3;
RA Kitamura K., Uyeda K., Hartman F.C., Kangawa K., Matsuo H.;
RT "Catalytic site of rat liver and bovine heart fructose-6-phosphate,2-
RT kinase:fructose-2,6-bisphosphatase. Identification of fructose 6-phosphate
RT binding site.";
RL J. Biol. Chem. 264:6344-6348(1989).
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: Phosphorylation results in the activation of the
CC kinase activity.
CC -!- SUBUNIT: Homodimer.
CC -!- TISSUE SPECIFICITY: Heart.
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; M34241; AAA30523.1; -; mRNA.
DR EMBL; S70453; AAB30689.2; -; mRNA.
DR PIR; S44388; A31780.
DR RefSeq; NP_777237.3; NM_174812.4.
DR PDB; 5HR5; X-ray; 1.82 A; A=1-531.
DR PDBsum; 5HR5; -.
DR AlphaFoldDB; P26285; -.
DR SMR; P26285; -.
DR BioGRID; 160003; 2.
DR ELM; P26285; -.
DR STRING; 9913.ENSBTAP00000002753; -.
DR iPTMnet; P26285; -.
DR PaxDb; P26285; -.
DR PRIDE; P26285; -.
DR Ensembl; ENSBTAT00000002753; ENSBTAP00000002753; ENSBTAG00000002126.
DR GeneID; 287019; -.
DR KEGG; bta:287019; -.
DR CTD; 5208; -.
DR VEuPathDB; HostDB:ENSBTAG00000002126; -.
DR VGNC; VGNC:32770; PFKFB2.
DR eggNOG; KOG0234; Eukaryota.
DR GeneTree; ENSGT00950000182835; -.
DR InParanoid; P26285; -.
DR OrthoDB; 392001at2759; -.
DR TreeFam; TF313541; -.
DR BRENDA; 2.7.1.105; 908.
DR BRENDA; 3.1.3.46; 908.
DR SABIO-RK; P26285; -.
DR Proteomes; UP000009136; Chromosome 16.
DR Bgee; ENSBTAG00000002126; Expressed in retina and 108 other tissues.
DR ExpressionAtlas; P26285; baseline and differential.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
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; 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 GO; GO:0006096; P:glycolytic process; ISS:UniProtKB.
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 3D-structure; Acetylation; ATP-binding; Direct protein sequencing;
KW Hydrolase; Kinase; Multifunctional enzyme; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:O60825"
FT CHAIN 2..531
FT /note="6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase
FT 2"
FT /id="PRO_0000179963"
FT REGION 2..249
FT /note="6-phosphofructo-2-kinase"
FT REGION 250..531
FT /note="Fructose-2,6-bisphosphatase"
FT REGION 446..531
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 446..482
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 129
FT /evidence="ECO:0000255"
FT ACT_SITE 159
FT /evidence="ECO:0000255"
FT ACT_SITE 258
FT /note="Tele-phosphohistidine intermediate"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT ACT_SITE 327
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
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 257
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 264
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 270
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 338
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 349..352
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P07953"
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 356
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 367
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 393..397
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P07953"
FT BINDING 393
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 397
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /evidence="ECO:0000250|UniProtKB:P07953"
FT BINDING 429
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT SITE 257
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT SITE 264
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT SITE 392
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 467
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:2846551"
FT MOD_RES 469
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O60825"
FT MOD_RES 476
FT /note="Phosphothreonine; by AMPK and PKC"
FT /evidence="ECO:0000269|PubMed:2846551"
FT MOD_RES 484
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O60825"
FT MOD_RES 494
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O60825"
FT HELIX 31..34
FT /evidence="ECO:0007829|PDB:5HR5"
FT STRAND 40..45
FT /evidence="ECO:0007829|PDB:5HR5"
FT HELIX 52..65
FT /evidence="ECO:0007829|PDB:5HR5"
FT STRAND 70..74
FT /evidence="ECO:0007829|PDB:5HR5"
FT HELIX 75..83
FT /evidence="ECO:0007829|PDB:5HR5"
FT HELIX 89..92
FT /evidence="ECO:0007829|PDB:5HR5"
FT HELIX 97..119
FT /evidence="ECO:0007829|PDB:5HR5"
FT STRAND 125..130
FT /evidence="ECO:0007829|PDB:5HR5"
FT HELIX 135..147
FT /evidence="ECO:0007829|PDB:5HR5"
FT STRAND 151..158
FT /evidence="ECO:0007829|PDB:5HR5"
FT HELIX 162..172
FT /evidence="ECO:0007829|PDB:5HR5"
FT TURN 173..175
FT /evidence="ECO:0007829|PDB:5HR5"
FT HELIX 184..201
FT /evidence="ECO:0007829|PDB:5HR5"
FT TURN 207..213
FT /evidence="ECO:0007829|PDB:5HR5"
FT STRAND 216..220
FT /evidence="ECO:0007829|PDB:5HR5"
FT TURN 221..224
FT /evidence="ECO:0007829|PDB:5HR5"
FT STRAND 225..229
FT /evidence="ECO:0007829|PDB:5HR5"
FT HELIX 234..243
FT /evidence="ECO:0007829|PDB:5HR5"
FT STRAND 253..257
FT /evidence="ECO:0007829|PDB:5HR5"
FT HELIX 262..266
FT /evidence="ECO:0007829|PDB:5HR5"
FT HELIX 277..293
FT /evidence="ECO:0007829|PDB:5HR5"
FT STRAND 299..302
FT /evidence="ECO:0007829|PDB:5HR5"
FT HELIX 306..313
FT /evidence="ECO:0007829|PDB:5HR5"
FT TURN 314..316
FT /evidence="ECO:0007829|PDB:5HR5"
FT HELIX 323..325
FT /evidence="ECO:0007829|PDB:5HR5"
FT HELIX 331..333
FT /evidence="ECO:0007829|PDB:5HR5"
FT HELIX 338..344
FT /evidence="ECO:0007829|PDB:5HR5"
FT HELIX 346..354
FT /evidence="ECO:0007829|PDB:5HR5"
FT TURN 356..358
FT /evidence="ECO:0007829|PDB:5HR5"
FT HELIX 367..383
FT /evidence="ECO:0007829|PDB:5HR5"
FT STRAND 385..391
FT /evidence="ECO:0007829|PDB:5HR5"
FT HELIX 393..404
FT /evidence="ECO:0007829|PDB:5HR5"
FT TURN 408..410
FT /evidence="ECO:0007829|PDB:5HR5"
FT HELIX 411..413
FT /evidence="ECO:0007829|PDB:5HR5"
FT STRAND 420..427
FT /evidence="ECO:0007829|PDB:5HR5"
FT STRAND 430..437
FT /evidence="ECO:0007829|PDB:5HR5"
SQ SEQUENCE 531 AA; 60811 MW; E5090BBFD10BC594 CRC64;
MSGNPASSSE QNNNSYETKA SLRISEKKCS WASYMTNSPT LIVMIGLPAR GKTYVSKKLT
RYLNWIGVPT KVFNLGVYRR QAVKSYKSYD FFRHDNEEAM KIRKQCALVA LKDVKAYLTE
ESGQIAVFDA TNTTRERRDL ILNFAEENSF KVFFVESVCD DPDVIAANIL EVKVSSPDYP
ERNRENVMDD FLKRIECYKV TYQPLDPDSH DKDLSFIKVI NVGQRFLVNK VQDYIQSKIV
YYLMNIHVHP RTIYLCRHGE SEFNLLGKIG GDSGLSVRGK QFAQALRKFL EEQEIADLKV
WTSQLKRTIQ TAESLGVTYE QWKILNEIDA GVCEEMTYAE IQEQYPDEFA LRDEEKYLYR
YPGGESYQDL VQRLEPVIME LERQGNVLVI SHQAVMRCLL AYFLDKGADE LPYLRCPLHT
IFKLTPVAYG CKVETIKLNV EAVNTHRDKP TNNFPKSQTP VRMRRNSFTP LSSSNTIRRP
RNYSVGSRPL QPLSPLRALD TQEGADQPKT QAETSRAAHR LPSPAPPTSP S
