ID PFKAP_RAT Reviewed; 788 AA.
AC P47860; Q5HZX8;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 20-DEC-2005, sequence version 2.
DT 24-JAN-2024, entry version 165.
DE RecName: Full=ATP-dependent 6-phosphofructokinase, platelet type {ECO:0000255|HAMAP-Rule:MF_03184};
DE Short=ATP-PFK {ECO:0000255|HAMAP-Rule:MF_03184};
DE Short=PFK-P;
DE EC=2.7.1.11 {ECO:0000255|HAMAP-Rule:MF_03184};
DE AltName: Full=6-phosphofructokinase type C;
DE AltName: Full=Phosphofructo-1-kinase isozyme C;
DE Short=PFK-C;
DE AltName: Full=Phosphohexokinase {ECO:0000255|HAMAP-Rule:MF_03184};
GN Name=Pfkp; Synonyms=Pfkc;
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 [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 3-788.
RC TISSUE=Hypothalamus;
RX PubMed=8106374; DOI=10.1016/s0021-9258(17)41869-2;
RA Gekakis N., Johnson R.C., Jerkins A., Mains R.E., Sul H.S.;
RT "Structure, distribution, and functional expression of the
RT phosphofructokinase C isozyme.";
RL J. Biol. Chem. 269:3348-3355(1994).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2; SER-142 AND SER-386, 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: Catalyzes the phosphorylation of D-fructose 6-phosphate to
CC fructose 1,6-bisphosphate by ATP, the first committing step of
CC glycolysis. {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 {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). Interacts with ATG4B; promoting phosphorylation of
CC ATG4B. {ECO:0000255|HAMAP-Rule:MF_03184, ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03184}.
CC -!- TISSUE SPECIFICITY: Expressed at high level in neuroendocrine tissues.
CC -!- PTM: GlcNAcylation decreases enzyme activity. {ECO:0000250}.
CC -!- PTM: Phosphorylation at Ser-386 promotes interaction with ATG4B.
CC {ECO:0000250|UniProtKB:Q01813}.
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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA17757.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; BC088847; AAH88847.1; -; mRNA.
DR EMBL; L25387; AAA17757.1; ALT_FRAME; mRNA.
DR PIR; A53047; A53047.
DR RefSeq; NP_996729.1; NM_206847.1.
DR AlphaFoldDB; P47860; -.
DR SMR; P47860; -.
DR BioGRID; 248822; 4.
DR ComplexPortal; CPX-2054; 6-phosphofructokinase, P4 homotetramer.
DR IntAct; P47860; 5.
DR MINT; P47860; -.
DR STRING; 10116.ENSRNOP00000023252; -.
DR GlyCosmos; P47860; 1 site, No reported glycans.
DR GlyGen; P47860; 2 sites, 1 O-linked glycan (1 site).
DR iPTMnet; P47860; -.
DR PhosphoSitePlus; P47860; -.
DR World-2DPAGE; 0004:P47860; -.
DR jPOST; P47860; -.
DR PaxDb; 10116-ENSRNOP00000023252; -.
DR Ensembl; ENSRNOT00000023252.8; ENSRNOP00000023252.8; ENSRNOG00000017163.8.
DR Ensembl; ENSRNOT00055010648; ENSRNOP00055008257; ENSRNOG00055006544.
DR Ensembl; ENSRNOT00060026666; ENSRNOP00060021340; ENSRNOG00060015533.
DR Ensembl; ENSRNOT00065005398; ENSRNOP00065003925; ENSRNOG00065003704.
DR GeneID; 60416; -.
DR KEGG; rno:60416; -.
DR UCSC; RGD:61893; rat.
DR AGR; RGD:61893; -.
DR CTD; 5214; -.
DR RGD; 61893; Pfkp.
DR eggNOG; KOG2440; Eukaryota.
DR GeneTree; ENSGT00940000155002; -.
DR InParanoid; P47860; -.
DR OrthoDB; 374214at2759; -.
DR PhylomeDB; P47860; -.
DR Reactome; R-RNO-70171; Glycolysis.
DR SABIO-RK; P47860; -.
DR UniPathway; UPA00109; UER00182.
DR PRO; PR:P47860; -.
DR Proteomes; UP000002494; Chromosome 17.
DR GO; GO:0005945; C:6-phosphofructokinase complex; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005829; C:cytosol; ISO: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:0070095; F:fructose-6-phosphate binding; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; IPI:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0048029; F:monosaccharide binding; IBA:GO_Central.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:RGD.
DR GO; GO:0061621; P:canonical glycolysis; IBA:GO_Central.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; ISO: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 CDD; cd00764; Eukaryotic_PFK; 1.
DR Gene3D; 3.40.50.450; -; 2.
DR Gene3D; 3.40.50.460; Phosphofructokinase domain; 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 NCBIfam; TIGR02478; 6PF1K_euk; 1.
DR PANTHER; PTHR13697:SF5; ATP-DEPENDENT 6-PHOSPHOFRUCTOKINASE, PLATELET TYPE; 1.
DR PANTHER; PTHR13697; PHOSPHOFRUCTOKINASE; 1.
DR Pfam; PF00365; PFK; 2.
DR PIRSF; PIRSF000533; ATP_PFK_euk; 1.
DR PRINTS; PR00476; PHFRCTKINASE.
DR SUPFAM; SSF53784; Phosphofructokinase; 2.
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 CHAIN 1..788
FT /note="ATP-dependent 6-phosphofructokinase, platelet type"
FT /id="PRO_0000112027"
FT REGION 1..399
FT /note="N-terminal catalytic PFK domain 1"
FT REGION 400..411
FT /note="Interdomain linker"
FT REGION 412..788
FT /note="C-terminal regulatory PFK domain 2"
FT ACT_SITE 175
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 34
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 97..98
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 127..130
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 128
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 173..175
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 210
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 217..219
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 273
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 301
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 307..310
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 481
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 538..542
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 576
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 583..585
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 639
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 665
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 671..674
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 744
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 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q01813"
FT MOD_RES 2
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 6
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q01813"
FT MOD_RES 12
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P47859"
FT MOD_RES 21
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q01813"
FT MOD_RES 142
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 386
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 395
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q01813"
FT MOD_RES 486
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q01813"
FT MOD_RES 651
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q01813"
FT MOD_RES 688
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q01813"
FT CARBOHYD 540
FT /note="O-linked (GlcNAc) serine"
FT /evidence="ECO:0000250"
FT CONFLICT 35..36
FT /note="DA -> ES (in Ref. 2; AAA17757)"
FT /evidence="ECO:0000305"
FT CONFLICT 51
FT /note="I -> M (in Ref. 2; AAA17757)"
FT /evidence="ECO:0000305"
FT CONFLICT 56
FT /note="K -> Q (in Ref. 2; AAA17757)"
FT /evidence="ECO:0000305"
FT CONFLICT 111
FT /note="A -> T (in Ref. 2; AAA17757)"
FT /evidence="ECO:0000305"
FT CONFLICT 220
FT /note="H -> Y (in Ref. 2; AAA17757)"
FT /evidence="ECO:0000305"
FT CONFLICT 600
FT /note="A -> R (in Ref. 2; AAA17757)"
FT /evidence="ECO:0000305"
FT CONFLICT 755
FT /note="R -> L (in Ref. 2; AAA17757)"
FT /evidence="ECO:0000305"
FT CONFLICT 758
FT /note="M -> S (in Ref. 2; AAA17757)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 788 AA; 85720 MW; 16FEB963C3297CA6 CRC64;
MSDQDSSTSS TSFPKYLEHL SGDGKAIGVL TSGGDAQGMN AAVRAVVRMG IYTGAKVYFI
YEGYQGMVDG GSNIVEAKWE CVSSILQVGG TIIGSARCQA FRSREGRLKA ACNLVRLGIT
NLCVIGGDGS LTGANLFRKE WSGLLEELAK NGEIDSDTVK KHAYLNVVGM VGSIDNDFCG
TDMTIGTDSA LHRIIEVVDA IMTTAQSHQR TFVLEVMGRH CGYLALVSAL ACGADWVFLP
ESPPEEGWEE EMCLKLSENR ARKKRLNIII VSEGAIDTQN KPITSEKIKE LVVTNLGFDT
RVTILGHVQR GGTPSAFDRI LASRMGVEAV LALLEATPET PACVVSLRGN QAVRLPLMEC
VQMTQDVQKA MDERRFDEAV KLRGRSFEGN LNTYKRLAIK EPDDKIPKSN CNVAIINVGA
PAAGMNAAVR SAVRVGIAEG HKMFAIYDGF DGLANGQIKE IGWGDVGGWT GQGGSILGTK
RTLPGKYLEK IAEQMHSKNI NALLIIGGFE AYLGLLELAA ARNKHEAFCV PMVMVPATVS
NNVPGSDFSI GADTALNTIT DTCDRIKQSA SGTKRRVFII ETMGGYCGYL ANMGGLAAGA
DAAYIFEEQF DIRDLQSNVM HLTEKMKTSI QRGLVLRNEN CSVNYTTDFI YQLYSEEGKG
VFDCRKNVLG HMQQGGAPSP FDRNFGTKIS AKAMEWISAK LKGSHGTGKK FVSDDSICVL
GIQKRDLLFK PVAELRKATD FEHRIPKQQW WLKLRPIMKI LAKYEASYDM SDVGKLEPVH
NHGELSAI
//
