PFKAM_RAT
ID PFKAM_RAT Reviewed; 780 AA.
AC P47858; Q63736;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=ATP-dependent 6-phosphofructokinase, muscle type {ECO:0000255|HAMAP-Rule:MF_03184};
DE Short=ATP-PFK {ECO:0000255|HAMAP-Rule:MF_03184};
DE Short=PFK-M;
DE EC=2.7.1.11 {ECO:0000255|HAMAP-Rule:MF_03184};
DE AltName: Full=6-phosphofructokinase type A;
DE AltName: Full=Phosphofructo-1-kinase isozyme A;
DE Short=PFK-A;
DE AltName: Full=Phosphohexokinase {ECO:0000255|HAMAP-Rule:MF_03184};
GN Name=Pfkm; Synonyms=Pfk-m;
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=Pancreatic islet;
RX PubMed=8764833; DOI=10.1016/0167-4781(96)00088-7;
RA Ma Z., Ramanadham S., Turk J., Kempe K., Hu Z., Ladenson J.;
RT "Characterization of expression of phosphofructokinase isoforms in isolated
RT rat pancreatic islets and purified beta cells and cloning and expression of
RT the rat phosphofructokinase-A isoform.";
RL Biochim. Biophys. Acta 1308:151-163(1996).
RN [2]
RP SEQUENCE REVISION TO 163-170 AND 494-498.
RA Ma Z.;
RL Submitted (SEP-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 8-213.
RC STRAIN=Sprague-Dawley;
RA Nakajima H.;
RL Submitted (NOV-1993) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-133; SER-377 AND SER-775, 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 (via C-terminus) with HK1 (via N-terminal
CC spermatogenic cell-specific region) (By similarity).
CC {ECO:0000250|UniProtKB:P47857, ECO:0000255|HAMAP-Rule:MF_03184,
CC ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03184}.
CC -!- PTM: GlcNAcylation decreases enzyme activity. {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; U25651; AAC52786.1; -; mRNA.
DR EMBL; D21869; BAA21013.1; -; mRNA.
DR PIR; S71429; S71429.
DR RefSeq; NP_113903.1; NM_031715.1.
DR AlphaFoldDB; P47858; -.
DR SMR; P47858; -.
DR BioGRID; 249268; 6.
DR ComplexPortal; CPX-2050; 6-phosphofructokinase, M4 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; P47858; 4.
DR MINT; P47858; -.
DR STRING; 10116.ENSRNOP00000013374; -.
DR GlyGen; P47858; 1 site.
DR iPTMnet; P47858; -.
DR PhosphoSitePlus; P47858; -.
DR jPOST; P47858; -.
DR PaxDb; P47858; -.
DR PRIDE; P47858; -.
DR GeneID; 65152; -.
DR KEGG; rno:65152; -.
DR UCSC; RGD:68419; rat.
DR CTD; 5213; -.
DR RGD; 68419; Pfkm.
DR eggNOG; KOG2440; Eukaryota.
DR InParanoid; P47858; -.
DR OrthoDB; 172878at2759; -.
DR PhylomeDB; P47858; -.
DR BRENDA; 2.7.1.11; 5301.
DR Reactome; R-RNO-70171; Glycolysis.
DR SABIO-RK; P47858; -.
DR UniPathway; UPA00109; UER00182.
DR PRO; PR:P47858; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005945; C:6-phosphofructokinase complex; ISO:RGD.
DR GO; GO:0016324; C:apical plasma membrane; ISO:RGD.
DR GO; GO:0005829; C:cytosol; ISO:RGD.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0097228; C:sperm principal piece; ISO:RGD.
DR GO; GO:0003872; F:6-phosphofructokinase activity; IDA:RGD.
DR GO; GO:0016208; F:AMP binding; IDA:RGD.
DR GO; GO:0005524; F:ATP binding; IDA:RGD.
DR GO; GO:0030246; F:carbohydrate binding; IDA:RGD.
DR GO; GO:0070061; F:fructose binding; ISO: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; IBA:GO_Central.
DR GO; GO:0008443; F:phosphofructokinase activity; IMP:RGD.
DR GO; GO:0008022; F:protein C-terminus binding; ISO:RGD.
DR GO; GO:0061621; P:canonical glycolysis; ISO:RGD.
DR GO; GO:0001678; P:cellular glucose homeostasis; NAS: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:0042593; P:glucose homeostasis; ISO:RGD.
DR GO; GO:0005980; P:glycogen catabolic process; ISO:RGD.
DR GO; GO:0093001; P:glycolysis from storage polysaccharide through glucose-1-phosphate; ISO: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:0046716; P:muscle cell cellular homeostasis; ISO:RGD.
DR GO; GO:0032024; P:positive regulation of insulin secretion; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
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; Hydroxylation; Kinase; Magnesium; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P00511"
FT CHAIN 2..780
FT /note="ATP-dependent 6-phosphofructokinase, muscle type"
FT /id="PRO_0000112020"
FT REGION 2..390
FT /note="N-terminal catalytic PFK domain 1"
FT REGION 391..401
FT /note="Interdomain linker"
FT REGION 402..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 471
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 528..532
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 566
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 573..575
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 629
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 655
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 661..664
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 735
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-acetylthreonine"
FT /evidence="ECO:0000250|UniProtKB:P00511"
FT MOD_RES 133
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 377
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 557
FT /note="N6-(2-hydroxyisobutyryl)lysine"
FT /evidence="ECO:0000250|UniProtKB:P08237"
FT MOD_RES 775
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT CARBOHYD 530
FT /note="O-linked (GlcNAc) serine"
FT /evidence="ECO:0000250"
FT CONFLICT 33
FT /note="T -> A (in Ref. 3; BAA21013)"
FT /evidence="ECO:0000305"
FT CONFLICT 46
FT /note="L -> A (in Ref. 3; BAA21013)"
FT /evidence="ECO:0000305"
FT CONFLICT 150
FT /note="R -> A (in Ref. 3; BAA21013)"
FT /evidence="ECO:0000305"
FT CONFLICT 160
FT /note="F -> G (in Ref. 3; BAA21013)"
FT /evidence="ECO:0000305"
FT CONFLICT 180
FT /note="S -> F (in Ref. 3; BAA21013)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 780 AA; 85560 MW; CECC3995C4F271FA CRC64;
MTHEEHHEAK TLGIGKAIAV LTSGGDAQGM NATVRAVVRV GIFTGLRVFF VHEGYQGLVD
GGEHIREATW ESVSMMLQLG GTVIGSARCK DFREREGRLR AAHNLVKRGI TNLCVIGGDG
SLTGADTFRS EWSDLLNDLQ KDGKITAEER TKSSYLNIVF LVGSIDNDFC GTDMTIGTDS
ALHRIVEIVD AITTTAQSHQ RTFVLEVMGR HCGYLALVTS LSCGADWVFI PECPPDDDWE
EHLCRRLSET RTRGSRLNII IVAEGAIDKN GKPITSEDIK NLVVKRLGYD TRVTVLGHVQ
RGGTPSAFDR ILGSRMGVEA VMALLEGTPD TPACVVSLSG NTAVRLPLME CVQVTKDVTK
AMDEKRFDEA IKLRGRSFMN NWEVYKLLAH VRPPVSKGGL HTVAVMNVGA PAAGMNAAVR
STVRIGLIQG NRVLVVHDGF EGLAKGQIEE AGWSYVGGWT GQGGSKLGTK RTLPKKNLEQ
ISANITKYNI QGLVIIGGFE AYTGGLELME GRKQFDELCI PFVVIPATVS NNVPGSDFSI
GADTALNTIC TTCDRIKQSA AGTKRRVFII ETMGGYCGYL ATMAGLAAGA DAAYIFEEPF
TIRDLQVNVE HLVQKMKTTV KRGLVLRNEK CNENYTTDFI FNLYSEEGKG IFDSRKNVLG
HMQQGGNPTP FDRNFATKMG AKATNWMSGK IKESYRNGRI FANTPDSGCV LGMRKRALVF
QPVTELKDQT DFEHRIPKEQ WWLKLRPILK ILAKYEIDLD TSDHAHLEHI SRKRSGEAAV
