PFKAL_RAT
ID PFKAL_RAT Reviewed; 780 AA.
AC P30835;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=ATP-dependent 6-phosphofructokinase, liver type {ECO:0000255|HAMAP-Rule:MF_03184};
DE Short=ATP-PFK {ECO:0000255|HAMAP-Rule:MF_03184};
DE Short=PFK-L;
DE EC=2.7.1.11 {ECO:0000255|HAMAP-Rule:MF_03184};
DE AltName: Full=6-phosphofructokinase type B;
DE AltName: Full=Phosphofructo-1-kinase isozyme B;
DE Short=PFK-B;
DE AltName: Full=Phosphohexokinase {ECO:0000255|HAMAP-Rule:MF_03184};
GN Name=Pfkl; Synonyms=Pfk-l;
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=Liver;
RX PubMed=1836995; DOI=10.1111/j.1432-1033.1991.tb16375.x;
RA Hotta K., Nakajima H., Yamasaki T., Hamaguchi T., Kuwajima M., Noguchi T.,
RA Tanaka T., Kono N., Tarui S.;
RT "Rat-liver-type phosphofructokinase mRNA. Structure, tissue distribution
RT and regulation.";
RL Eur. J. Biochem. 202:293-298(1991).
RN [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-775, AND IDENTIFICATION BY
RP 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: Catalyzes the phosphorylation of D-fructose 6-phosphate to
CC fructose 1,6-bisphosphate by ATP, the first committing step of
CC glycolysis (By similarity). Negatively regulates the phagocyte
CC oxidative burst in response to bacterial infection by controlling
CC cellular NADPH biosynthesis and NADPH oxidase-derived reactive oxygen
CC species. Upon macrophage activation, drives the metabolic switch toward
CC glycolysis, thus preventing glucose turnover that produces NADPH via
CC pentose phosphate pathway (By similarity).
CC {ECO:0000250|UniProtKB:P12382, ECO:0000255|HAMAP-Rule:MF_03184}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + beta-D-fructose 6-phosphate = ADP + beta-D-fructose 1,6-
CC bisphosphate + H(+); Xref=Rhea:RHEA:16109, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:32966, ChEBI:CHEBI:57634,
CC ChEBI:CHEBI:456216; EC=2.7.1.11; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_03184};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC -!- ACTIVITY REGULATION: Allosterically activated by ADP, AMP, or fructose
CC 2,6-bisphosphate, and allosterically inhibited by ATP or citrate.
CC GlcNAcylation by OGT overcomes allosteric regulation (By similarity).
CC {ECO:0000255|HAMAP-Rule:MF_03184}.
CC -!- PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-
CC phosphate and glycerone phosphate from D-glucose: step 3/4.
CC {ECO:0000255|HAMAP-Rule:MF_03184}.
CC -!- SUBUNIT: Homo- and heterotetramers (By similarity). Phosphofructokinase
CC (PFK) enzyme functions as a tetramer composed of different combinations
CC of 3 types of subunits, called PFKM (M), PFKL (L) and PFKP (P). The
CC composition of the PFK tetramer differs according to the tissue type it
CC is present in. The kinetic and regulatory properties of the tetrameric
CC enzyme are dependent on the subunit composition, hence can vary across
CC tissues (Probable). {ECO:0000255|HAMAP-Rule:MF_03184, ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03184}.
CC -!- PTM: GlcNAcylation at Ser-529 by OGT decreases enzyme activity, leading
CC to redirect glucose flux through the oxidative pentose phosphate
CC pathway. Glycosylation is stimulated by both hypoxia and glucose
CC deprivation (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the phosphofructokinase type A (PFKA) family.
CC ATP-dependent PFK group I subfamily. Eukaryotic two domain clade 'E'
CC sub-subfamily. {ECO:0000255|HAMAP-Rule:MF_03184}.
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DR EMBL; X58865; CAA41674.1; -; mRNA.
DR PIR; S19689; S19689.
DR RefSeq; NP_037322.1; NM_013190.4.
DR AlphaFoldDB; P30835; -.
DR SMR; P30835; -.
DR BioGRID; 247769; 2.
DR ComplexPortal; CPX-2051; 6-phosphofructokinase, L4 homotetramer.
DR ComplexPortal; CPX-2058; 6-phosphofructokinase, ML3 heterotetramer.
DR ComplexPortal; CPX-2059; 6-phosphofructokinase, M2L2 heterotetramer.
DR ComplexPortal; CPX-2060; 6-phosphofructokinase, M3L heterotetramer.
DR IntAct; P30835; 1.
DR STRING; 10116.ENSRNOP00000001625; -.
DR BindingDB; P30835; -.
DR ChEMBL; CHEMBL4739847; -.
DR GlyGen; P30835; 1 site.
DR iPTMnet; P30835; -.
DR PhosphoSitePlus; P30835; -.
DR jPOST; P30835; -.
DR PaxDb; P30835; -.
DR PRIDE; P30835; -.
DR Ensembl; ENSRNOT00000001625; ENSRNOP00000001625; ENSRNOG00000001214.
DR GeneID; 25741; -.
DR KEGG; rno:25741; -.
DR UCSC; RGD:3311; rat.
DR CTD; 5211; -.
DR RGD; 3311; Pfkl.
DR eggNOG; KOG2440; Eukaryota.
DR GeneTree; ENSGT00940000159292; -.
DR HOGENOM; CLU_011053_0_0_1; -.
DR InParanoid; P30835; -.
DR OMA; WFNLRPM; -.
DR OrthoDB; 172878at2759; -.
DR PhylomeDB; P30835; -.
DR TreeFam; TF300411; -.
DR Reactome; R-RNO-6798695; Neutrophil degranulation.
DR Reactome; R-RNO-70171; Glycolysis.
DR SABIO-RK; P30835; -.
DR UniPathway; UPA00109; UER00182.
DR PRO; PR:P30835; -.
DR Proteomes; UP000002494; Chromosome 20.
DR Bgee; ENSRNOG00000001214; Expressed in frontal cortex and 19 other tissues.
DR Genevisible; P30835; RN.
DR GO; GO:0005945; C:6-phosphofructokinase complex; ISO:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0003872; F:6-phosphofructokinase activity; IDA:RGD.
DR GO; GO:0016208; F:AMP binding; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IDA:RGD.
DR GO; GO:0070061; F:fructose binding; ISO:RGD.
DR GO; GO:0004331; F:fructose-2,6-bisphosphate 2-phosphatase activity; TAS:RGD.
DR GO; GO:0070095; F:fructose-6-phosphate binding; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; IPI:RGD.
DR GO; GO:0019900; F:kinase binding; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0048029; F:monosaccharide binding; IDA:RGD.
DR GO; GO:0061621; P:canonical glycolysis; IBA:GO_Central.
DR GO; GO:0005975; P:carbohydrate metabolic process; IDA:RGD.
DR GO; GO:0030388; P:fructose 1,6-bisphosphate metabolic process; IDA:RGD.
DR GO; GO:0006002; P:fructose 6-phosphate metabolic process; IDA:RGD.
DR GO; GO:0006096; P:glycolytic process; IDA:RGD.
DR GO; GO:0061615; P:glycolytic process through fructose-6-phosphate; ISO:RGD.
DR GO; GO:0046676; P:negative regulation of insulin secretion; ISO:RGD.
DR GO; GO:0009749; P:response to glucose; ISS:UniProtKB.
DR CDD; cd00764; Eukaryotic_PFK; 1.
DR Gene3D; 3.40.50.460; -; 2.
DR HAMAP; MF_03184; Phosphofructokinase_I_E; 1.
DR InterPro; IPR009161; 6-Pfructokinase_euk.
DR InterPro; IPR022953; ATP_PFK.
DR InterPro; IPR041914; PFK_vert-type.
DR InterPro; IPR015912; Phosphofructokinase_CS.
DR InterPro; IPR000023; Phosphofructokinase_dom.
DR InterPro; IPR035966; PKF_sf.
DR Pfam; PF00365; PFK; 2.
DR PIRSF; PIRSF000533; ATP_PFK_euk; 1.
DR PRINTS; PR00476; PHFRCTKINASE.
DR SUPFAM; SSF53784; SSF53784; 2.
DR TIGRFAMs; TIGR02478; 6PF1K_euk; 1.
DR PROSITE; PS00433; PHOSPHOFRUCTOKINASE; 2.
PE 1: Evidence at protein level;
KW Acetylation; Allosteric enzyme; ATP-binding; Cytoplasm; Glycolysis;
KW Glycoprotein; Kinase; Magnesium; Metal-binding; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P17858"
FT CHAIN 2..780
FT /note="ATP-dependent 6-phosphofructokinase, liver type"
FT /id="PRO_0000112023"
FT REGION 2..390
FT /note="N-terminal catalytic PFK domain 1"
FT REGION 391..400
FT /note="Interdomain linker"
FT REGION 401..780
FT /note="C-terminal regulatory PFK domain 2"
FT ACT_SITE 166
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 25
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 88..89
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 118..121
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 119
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 164..166
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 201
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 208..210
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 264
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 292
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 298..301
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 470
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /ligand_note="allosteric activator; ligand shared between
FT dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 527..531
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /ligand_note="allosteric activator; ligand shared between
FT dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 565
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /ligand_note="allosteric activator; ligand shared between
FT dimeric partners"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 572..574
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /ligand_note="allosteric activator; ligand shared between
FT dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 628
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /ligand_note="allosteric activator; ligand shared between
FT dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 654
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /ligand_note="allosteric activator; ligand shared between
FT dimeric partners"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 660..663
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /ligand_note="allosteric activator; ligand shared between
FT dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 734
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /ligand_note="allosteric activator; ligand shared between
FT dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:P17858"
FT MOD_RES 377
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P47857"
FT MOD_RES 640
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P12382"
FT MOD_RES 775
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT CARBOHYD 529
FT /note="O-linked (GlcNAc) serine"
FT /evidence="ECO:0000250"
SQ SEQUENCE 780 AA; 85339 MW; 7F6FCFB076D6A0F1 CRC64;
MATVDLEKLR MSGAGKAIGV LTSGGDAQGM NAAVRAVTRM GIYVGAKVFL IYEGYEGLVE
GGENIKPANW LSVSNIIQLG GTIIGSARCK AFTTREGRLA AAYNLLQHGI TNLCVIGGDG
SLTGANIFRN EWGSLLEELV KEGKISESTA QNYAHLSIAG LVGSIDNDFC GTDMTIGTDS
ALHRIMEVID AITTTAQSHQ RTFVLEVMGR HCGYLALVSA LASGADWLFI PEAPPEDGWE
NFMCERLGET RSRGSRLNII IIAEGAIDRH GKPISSSYVK DLVVQRLGFD TRVTVLGHVQ
RGGTPSAFDR VLSSKMGMEA VMALLEATPD TPACVVSLSG NQSVRLPLME CVQVTKDVQK
AMDEKRFDEA IQLRGRSFEN NWKIYKLLAH QKVSKEKSNF SLAILNVGAP AAGMNAAVRS
AVRTGISEGH TVYVVHDGFE GLAKGQVQEV GWHDVAGWLG RGGSMLGTKR TLPKPHLEAI
VENLRTYNIH ALLVIGGFEA YEGVLQLVEA RGRYEELCIV MCVIPATISN NVPGTDFSLG
SDTAVNAAME SCDRIKQSAS GTKRRVFIVE TMGGYCGYLA TVTGIAVGAD AAYVFEDPFN
IHDLKANVEH MTEKMKTDIQ RGLVLRNEKC HEHYTTEFLY NLYSSEGRGV FDCRTNVLGH
LQQGGAPTPF DRNYGTKLGV KAMLWMSEKL RDVYRKGRVF ANAPDSACVI GLRKKVVAFS
SVTELKKETD FEHRMPREQW WLNLRLMLKM LAHYRISMAD YVSGELEHVT RRTLSIDKGF
