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Database: UniProt/SWISS-PROT
Entry: PFKAL_RAT
LinkDB: PFKAL_RAT
Original site: 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   16-JAN-2019, entry version 163.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
OC   Muroidea; Muridae; 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.,
RA   Noguchi T., Tanaka T., Kono N., Tarui S.;
RT   "Rat-liver-type phosphofructokinase mRNA. Structure, tissue
RT   distribution and regulation.";
RL   Eur. J. Biochem. 202:293-298(1991).
RN   [2]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-775, AND IDENTIFICATION
RP   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.,
RA   Lundby C., Olsen J.V.;
RT   "Quantitative maps of protein phosphorylation sites across 14
RT   different rat organs and tissues.";
RL   Nat. Commun. 3:876-876(2012).
CC   -!- FUNCTION: Catalyzes the phosphorylation of D-fructose 6-phosphate
CC       to 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
CC       oxygen species. Upon macrophage activation, drives the metabolic
CC       switch toward glycolysis, thus preventing glucose turnover that
CC       produces NADPH via 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
CC         1,6-bisphosphate + H(+); Xref=Rhea:RHEA:16109,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:32966,
CC         ChEBI:CHEBI:57634, ChEBI:CHEBI:456216; EC=2.7.1.11;
CC         Evidence={ECO:0000255|HAMAP-Rule:MF_03184};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC   -!- ACTIVITY REGULATION: Allosterically activated by ADP, AMP, or
CC       fructose 2,6-bisphosphate, and allosterically inhibited by ATP or
CC       citrate. GlcNAcylation by OGT overcomes allosteric regulation (By
CC       similarity). {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).
CC       Phosphofructokinase (PFK) enzyme functions as a tetramer composed
CC       of different combinations of 3 types of subunits, called PFKM (M),
CC       PFKL (L) and PFKP (P). The composition of the PFK tetramer differs
CC       according to the tissue type it is present in. The kinetic and
CC       regulatory properties of the tetrameric enzyme are dependent on
CC       the subunit composition, hence can vary across tissues (Probable).
CC       {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,
CC       leading to redirect glucose flux through the oxidative pentose
CC       phosphate pathway. Glycosylation is stimulated by both hypoxia and
CC       glucose deprivation (By similarity). {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the phosphofructokinase type A (PFKA)
CC       family. ATP-dependent PFK group I subfamily. Eukaryotic two domain
CC       clade "E" sub-subfamily. {ECO:0000255|HAMAP-Rule:MF_03184}.
DR   EMBL; X58865; CAA41674.1; -; mRNA.
DR   PIR; S19689; S19689.
DR   RefSeq; NP_037322.1; NM_013190.4.
DR   UniGene; Rn.4212; -.
DR   ProteinModelPortal; P30835; -.
DR   SMR; P30835; -.
DR   BioGrid; 247769; 1.
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   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   eggNOG; COG0205; LUCA.
DR   GeneTree; ENSGT00940000159292; -.
DR   HOGENOM; HOG000200154; -.
DR   HOVERGEN; HBG000976; -.
DR   InParanoid; P30835; -.
DR   KO; K00850; -.
DR   OMA; DPFNIQD; -.
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 10 organ(s), highest expression level in brain.
DR   Genevisible; P30835; RN.
DR   GO; GO:0005945; C:6-phosphofructokinase complex; IBA:GO_Central.
DR   GO; GO:0005829; C:cytosol; IDA:RGD.
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; IEA:Ensembl.
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; IBA:GO_Central.
DR   GO; GO:0019900; F:kinase binding; IEA:Ensembl.
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:0006007; P:glucose catabolic process; IBA:GO_Central.
DR   GO; GO:0006096; P:glycolytic process; IDA:RGD.
DR   GO; GO:0046676; P:negative regulation of insulin secretion; IBA:GO_Central.
DR   GO; GO:0051259; P:protein complex oligomerization; IBA:GO_Central.
DR   GO; GO:0051289; P:protein homotetramerization; IDA:RGD.
DR   GO; GO:0009749; P:response to glucose; ISS:UniProtKB.
DR   HAMAP; MF_03184; Phosphofructokinase_I_E; 1.
DR   InterPro; IPR009161; 6-Pfructokinase_euk.
DR   InterPro; IPR022953; ATP_PFK.
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; Complete proteome;
KW   Cytoplasm; Glycolysis; Glycoprotein; Kinase; Magnesium; Metal-binding;
KW   Nucleotide-binding; Phosphoprotein; Reference proteome; Transferase.
FT   INIT_MET      1      1       Removed. {ECO:0000250|UniProtKB:P17858}.
FT   CHAIN         2    780       ATP-dependent 6-phosphofructokinase,
FT                                liver type.
FT                                /FTId=PRO_0000112023.
FT   NP_BIND      88     89       ATP. {ECO:0000255|HAMAP-Rule:MF_03184}.
FT   NP_BIND     118    121       ATP. {ECO:0000255|HAMAP-Rule:MF_03184}.
FT   REGION        2    390       N-terminal catalytic PFK domain 1.
FT   REGION      164    166       Substrate binding. {ECO:0000255|HAMAP-
FT                                Rule:MF_03184}.
FT   REGION      208    210       Substrate binding. {ECO:0000255|HAMAP-
FT                                Rule:MF_03184}.
FT   REGION      298    301       Substrate binding. {ECO:0000255|HAMAP-
FT                                Rule:MF_03184}.
FT   REGION      391    400       Interdomain linker.
FT   REGION      401    780       C-terminal regulatory PFK domain 2.
FT   REGION      527    531       Allosteric activator fructose 2,6-
FT                                bisphosphate binding. {ECO:0000255|HAMAP-
FT                                Rule:MF_03184}.
FT   REGION      572    574       Allosteric activator fructose 2,6-
FT                                bisphosphate binding. {ECO:0000255|HAMAP-
FT                                Rule:MF_03184}.
FT   REGION      660    663       Allosteric activator fructose 2,6-
FT                                bisphosphate binding. {ECO:0000255|HAMAP-
FT                                Rule:MF_03184}.
FT   ACT_SITE    166    166       Proton acceptor. {ECO:0000255|HAMAP-
FT                                Rule:MF_03184}.
FT   METAL       119    119       Magnesium; catalytic. {ECO:0000255|HAMAP-
FT                                Rule:MF_03184}.
FT   BINDING      25     25       ATP; via amide nitrogen.
FT                                {ECO:0000255|HAMAP-Rule:MF_03184}.
FT   BINDING     201    201       Substrate; shared with dimeric partner.
FT                                {ECO:0000255|HAMAP-Rule:MF_03184}.
FT   BINDING     264    264       Substrate. {ECO:0000255|HAMAP-
FT                                Rule:MF_03184}.
FT   BINDING     292    292       Substrate; shared with dimeric partner.
FT                                {ECO:0000255|HAMAP-Rule:MF_03184}.
FT   BINDING     470    470       Allosteric activator fructose 2,6-
FT                                bisphosphate. {ECO:0000255|HAMAP-
FT                                Rule:MF_03184}.
FT   BINDING     565    565       Allosteric activator fructose 2,6-
FT                                bisphosphate; shared with dimeric
FT                                partner. {ECO:0000255|HAMAP-
FT                                Rule:MF_03184}.
FT   BINDING     628    628       Allosteric activator fructose 2,6-
FT                                bisphosphate. {ECO:0000255|HAMAP-
FT                                Rule:MF_03184}.
FT   BINDING     654    654       Allosteric activator fructose 2,6-
FT                                bisphosphate; shared with dimeric
FT                                partner. {ECO:0000255|HAMAP-
FT                                Rule:MF_03184}.
FT   BINDING     734    734       Allosteric activator fructose 2,6-
FT                                bisphosphate. {ECO:0000255|HAMAP-
FT                                Rule:MF_03184}.
FT   MOD_RES       2      2       N-acetylalanine.
FT                                {ECO:0000250|UniProtKB:P17858}.
FT   MOD_RES     377    377       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P47857}.
FT   MOD_RES     640    640       Phosphotyrosine.
FT                                {ECO:0000250|UniProtKB:P12382}.
FT   MOD_RES     775    775       Phosphoserine.
FT                                {ECO:0000244|PubMed:22673903}.
FT   CARBOHYD    529    529       O-linked (GlcNAc) serine. {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
//
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