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Protein

ATP-dependent 6-phosphofructokinase, liver type

Gene

Pfkl

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate by ATP, the first committing step of glycolysis.

Catalytic activityi

ATP + D-fructose 6-phosphate = ADP + D-fructose 1,6-bisphosphate.UniRule annotation

Cofactori

Enzyme regulationi

Allosterically activated by ADP, AMP, or fructose 2,6-bisphosphate, and allosterically inhibited by ATP or citrate. GlcNAcylation by OGT overcomes allosteric regulation (By similarity).UniRule annotation

Pathwayi: glycolysis

This protein is involved in step 3 of the subpathway that synthesizes D-glyceraldehyde 3-phosphate and glycerone phosphate from D-glucose.UniRule annotation
Proteins known to be involved in the 4 steps of the subpathway in this organism are:
  1. no protein annotated in this organism
  2. Glucose-6-phosphate isomerase (Gpi), Glucose-6-phosphate isomerase (Gpi1), Glucose-6-phosphate isomerase (Gpi1), Glucose-6-phosphate isomerase (Gpi1)
  3. ATP-dependent 6-phosphofructokinase, liver type (Pfkl), ATP-dependent 6-phosphofructokinase (Pfkp), ATP-dependent 6-phosphofructokinase (Pfkm), ATP-dependent 6-phosphofructokinase, platelet type (Pfkp), ATP-dependent 6-phosphofructokinase, muscle type (Pfkm)
  4. Fructose-bisphosphate aldolase (Aldoart1), Fructose-bisphosphate aldolase (Aldoa), Fructose-bisphosphate aldolase (Aldoa), Fructose-bisphosphate aldolase (Aldoart2), Fructose-bisphosphate aldolase (Aldoart1), Fructose-bisphosphate aldolase (Aldoa), Fructose-bisphosphate aldolase (Aldoa), Fructose-bisphosphate aldolase (Aldob), Fructose-bisphosphate aldolase C (Aldoc), Fructose-bisphosphate aldolase A (Aldoa), Fructose-bisphosphate aldolase B (Aldob), Fructose-bisphosphate aldolase (Aldob)
This subpathway is part of the pathway glycolysis, which is itself part of Carbohydrate degradation.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes D-glyceraldehyde 3-phosphate and glycerone phosphate from D-glucose, the pathway glycolysis and in Carbohydrate degradation.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei25ATP; via amide nitrogenUniRule annotation1
Metal bindingi119Magnesium; catalyticUniRule annotation1
Active sitei166Proton acceptorUniRule annotation1
Binding sitei201Substrate; shared with dimeric partnerUniRule annotation1
Binding sitei264SubstrateUniRule annotation1
Binding sitei292Substrate; shared with dimeric partnerUniRule annotation1
Binding sitei470Allosteric activator fructose 2,6-bisphosphateUniRule annotation1
Binding sitei565Allosteric activator fructose 2,6-bisphosphate; shared with dimeric partnerUniRule annotation1
Binding sitei628Allosteric activator fructose 2,6-bisphosphateUniRule annotation1
Binding sitei654Allosteric activator fructose 2,6-bisphosphate; shared with dimeric partnerUniRule annotation1
Binding sitei734Allosteric activator fructose 2,6-bisphosphateUniRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi88 – 89ATPUniRule annotation2
Nucleotide bindingi118 – 121ATPUniRule annotation4

GO - Molecular functioni

GO - Biological processi

  • fructose 1,6-bisphosphate metabolic process Source: UniProtKB
  • fructose 6-phosphate metabolic process Source: MGI
  • glycolytic process Source: MGI
  • glycolytic process through fructose-6-phosphate Source: MGI
  • negative regulation of insulin secretion Source: MGI
  • protein homotetramerization Source: Ensembl
  • protein oligomerization Source: MGI
  • response to glucose Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase

Keywords - Biological processi

Glycolysis

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-6798695. Neutrophil degranulation.
R-MMU-70171. Glycolysis.
SABIO-RKP12382.
UniPathwayiUPA00109; UER00182.

Names & Taxonomyi

Protein namesi
Recommended name:
ATP-dependent 6-phosphofructokinase, liver typeUniRule annotation (EC:2.7.1.11UniRule annotation)
Short name:
ATP-PFKUniRule annotation
Short name:
PFK-L
Alternative name(s):
6-phosphofructokinase type B
Phosphofructo-1-kinase isozyme B
Short name:
PFK-B
PhosphohexokinaseUniRule annotation
Gene namesi
Name:Pfkl
Synonyms:Pfk-l, Pfkb
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:97547. Pfkl.

Subcellular locationi

  • Cytoplasm UniRule annotation

GO - Cellular componenti

  • 6-phosphofructokinase complex Source: MGI
  • cytosol Source: MGI
  • extracellular exosome Source: MGI
  • membrane Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00001120222 – 780ATP-dependent 6-phosphofructokinase, liver typeAdd BLAST779

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1
Modified residuei377PhosphoserineBy similarity1
Glycosylationi529O-linked (GlcNAc)By similarity1
Modified residuei640PhosphotyrosineCombined sources1
Modified residuei775PhosphoserineCombined sources1

Post-translational modificationi

GlcNAcylation at Ser-529 by OGT decreases enzyme activity, leading to redirect glucose flux through the oxidative pentose phosphate pathway. Glycosylation is stimulated by both hypoxia and glucose deprivation (By similarity).By similarity

Keywords - PTMi

Acetylation, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiP12382.
MaxQBiP12382.
PaxDbiP12382.
PeptideAtlasiP12382.
PRIDEiP12382.

PTM databases

iPTMnetiP12382.
PhosphoSitePlusiP12382.
SwissPalmiP12382.

Expressioni

Gene expression databases

BgeeiENSMUSG00000020277.
CleanExiMM_PFKL.
GenevisibleiP12382. MM.

Interactioni

Subunit structurei

Homo- and heterotetramers.

GO - Molecular functioni

Protein-protein interaction databases

BioGridi202124. 4 interactors.
IntActiP12382. 9 interactors.
MINTiMINT-135975.
STRINGi10090.ENSMUSP00000020522.

Structurei

3D structure databases

ProteinModelPortaliP12382.
SMRiP12382.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 390N-terminal catalytic PFK domain 1Add BLAST389
Regioni164 – 166Substrate bindingUniRule annotation3
Regioni208 – 210Substrate bindingUniRule annotation3
Regioni298 – 301Substrate bindingUniRule annotation4
Regioni391 – 400Interdomain linker10
Regioni401 – 780C-terminal regulatory PFK domain 2Add BLAST380
Regioni527 – 531Allosteric activator fructose 2,6-bisphosphate bindingUniRule annotation5
Regioni572 – 574Allosteric activator fructose 2,6-bisphosphate bindingUniRule annotation3
Regioni660 – 663Allosteric activator fructose 2,6-bisphosphate bindingUniRule annotation4

Sequence similaritiesi

Belongs to the phosphofructokinase type A (PFKA) family. ATP-dependent PFK group I subfamily. Eukaryotic two domain clade "E" sub-subfamily.UniRule annotation

Phylogenomic databases

eggNOGiKOG2440. Eukaryota.
COG0205. LUCA.
GeneTreeiENSGT00390000013209.
HOGENOMiHOG000200154.
HOVERGENiHBG000976.
InParanoidiP12382.
KOiK00850.
OMAiRTYSHLN.
OrthoDBiEOG091G01YN.
TreeFamiTF300411.

Family and domain databases

HAMAPiMF_03184. Phosphofructokinase_I_E. 1 hit.
InterProiIPR009161. 6-Pfructokinase_euk.
IPR022953. ATP_PFK.
IPR015912. Phosphofructokinase_CS.
IPR000023. Phosphofructokinase_dom.
[Graphical view]
PfamiPF00365. PFK. 2 hits.
[Graphical view]
PIRSFiPIRSF000533. ATP_PFK_euk. 1 hit.
PRINTSiPR00476. PHFRCTKINASE.
SUPFAMiSSF53784. SSF53784. 2 hits.
TIGRFAMsiTIGR02478. 6PF1K_euk. 1 hit.
PROSITEiPS00433. PHOSPHOFRUCTOKINASE. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P12382-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MATVDLEKLR MSGAGKAIGV LTSGGDAQGM NAAVRAVTRM GIYVGAKVFL
60 70 80 90 100
IYEGYEGLVE GGENIKPANW LSVSNIIQLG GTIIGSARCK AFTTREGRLA
110 120 130 140 150
AAYNLLQHGI TNLCVIGGDG SLTGANIFRN EWGSLLEELV KEGKISESTA
160 170 180 190 200
QNYAHLTIAG LVGSIDNDFC GTDMTIGTDS ALHRIMEVID AITTTAQSHQ
210 220 230 240 250
RTFVLEVMGR HCGYLALVSA LASGADWLFI PEAPPEDGWE NFMCERLGET
260 270 280 290 300
RSRGSRLNII IIAEGAIDRH GKPISSSYVK DLVVQRLGFD TRVTVLGHVQ
310 320 330 340 350
RGGTPSAFDR ILSSKMGMEA VMALLEATPD TPACVVSLSG NQSVRLPLME
360 370 380 390 400
CVQVTKDVQK AMDEERFDEA IQLRGRSFEN NWKIYKLLAH QKVSKEKSNF
410 420 430 440 450
SLAILNVGAP AAGMNAAVRS AVRTGISEGH TVYIVHDGFE GLAKGQVQEV
460 470 480 490 500
GWHDVAGWLG RGGSMLGTKR TLPKPHLEAI VENLRTYNIH ALLVIGGFEA
510 520 530 540 550
YEGVLQLVEA RGRYEELCIV MCVIPATISN NVPGTDFSLG SDTAVNAAME
560 570 580 590 600
SCDRIKQSAS GTKRRVFIVE TMGGYCGYLA TVTGIAVGAD AAYVFEDPFN
610 620 630 640 650
IHDLKANVEH MTEKMKTDIQ RGLVLRNEKC HEHYTTEFLY NLYSSEGRGV
660 670 680 690 700
FDCRTNVLGH LQQGGAPTPF DRNYGTKLGV KAMLWVSEKL RDVYRKGRVF
710 720 730 740 750
ANAPDSACVI GLRKKVVAFS PVTELKKETD FEHRMPREQW WLNLRLMLKM
760 770 780
LAHYRISMAD YVSGELEHVT RRTLSIDKGF
Length:780
Mass (Da):85,360
Last modified:July 27, 2011 - v4
Checksum:i0C12E2C222020B7F
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti419R → P in AAA20076 (PubMed:2969893).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J03928 mRNA. Translation: AAA20076.1.
AK030511 mRNA. Translation: BAC26997.1.
AK036318 mRNA. Translation: BAC29382.1.
AK081313 mRNA. Translation: BAC38193.1.
AK159328 mRNA. Translation: BAE34994.1.
CH466553 Genomic DNA. Translation: EDL31763.1.
BC020097 mRNA. Translation: AAH20097.1.
CCDSiCCDS35955.1.
PIRiA31070.
RefSeqiNP_032852.2. NM_008826.4.
UniGeneiMm.269649.

Genome annotation databases

EnsembliENSMUST00000020522; ENSMUSP00000020522; ENSMUSG00000020277.
GeneIDi18641.
KEGGimmu:18641.
UCSCiuc007fwo.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J03928 mRNA. Translation: AAA20076.1.
AK030511 mRNA. Translation: BAC26997.1.
AK036318 mRNA. Translation: BAC29382.1.
AK081313 mRNA. Translation: BAC38193.1.
AK159328 mRNA. Translation: BAE34994.1.
CH466553 Genomic DNA. Translation: EDL31763.1.
BC020097 mRNA. Translation: AAH20097.1.
CCDSiCCDS35955.1.
PIRiA31070.
RefSeqiNP_032852.2. NM_008826.4.
UniGeneiMm.269649.

3D structure databases

ProteinModelPortaliP12382.
SMRiP12382.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi202124. 4 interactors.
IntActiP12382. 9 interactors.
MINTiMINT-135975.
STRINGi10090.ENSMUSP00000020522.

PTM databases

iPTMnetiP12382.
PhosphoSitePlusiP12382.
SwissPalmiP12382.

Proteomic databases

EPDiP12382.
MaxQBiP12382.
PaxDbiP12382.
PeptideAtlasiP12382.
PRIDEiP12382.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000020522; ENSMUSP00000020522; ENSMUSG00000020277.
GeneIDi18641.
KEGGimmu:18641.
UCSCiuc007fwo.2. mouse.

Organism-specific databases

CTDi5211.
MGIiMGI:97547. Pfkl.

Phylogenomic databases

eggNOGiKOG2440. Eukaryota.
COG0205. LUCA.
GeneTreeiENSGT00390000013209.
HOGENOMiHOG000200154.
HOVERGENiHBG000976.
InParanoidiP12382.
KOiK00850.
OMAiRTYSHLN.
OrthoDBiEOG091G01YN.
TreeFamiTF300411.

Enzyme and pathway databases

UniPathwayiUPA00109; UER00182.
ReactomeiR-MMU-6798695. Neutrophil degranulation.
R-MMU-70171. Glycolysis.
SABIO-RKP12382.

Miscellaneous databases

PROiP12382.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000020277.
CleanExiMM_PFKL.
GenevisibleiP12382. MM.

Family and domain databases

HAMAPiMF_03184. Phosphofructokinase_I_E. 1 hit.
InterProiIPR009161. 6-Pfructokinase_euk.
IPR022953. ATP_PFK.
IPR015912. Phosphofructokinase_CS.
IPR000023. Phosphofructokinase_dom.
[Graphical view]
PfamiPF00365. PFK. 2 hits.
[Graphical view]
PIRSFiPIRSF000533. ATP_PFK_euk. 1 hit.
PRINTSiPR00476. PHFRCTKINASE.
SUPFAMiSSF53784. SSF53784. 2 hits.
TIGRFAMsiTIGR02478. 6PF1K_euk. 1 hit.
PROSITEiPS00433. PHOSPHOFRUCTOKINASE. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPFKAL_MOUSE
AccessioniPrimary (citable) accession number: P12382
Secondary accession number(s): Q8VDX7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: July 27, 2011
Last modified: November 30, 2016
This is version 161 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Allosteric enzyme, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.