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P17858 (K6PL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 170. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
6-phosphofructokinase, liver type

EC=2.7.1.11
Alternative name(s):
Phosphofructo-1-kinase isozyme B
Short name=PFK-B
Phosphofructokinase 1
Phosphohexokinase
Gene names
Name:PFKL
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length780 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalyzes the third step of glycolysis, the phosphorylation of fructose-6-phosphate (F6P) by ATP to generate fructose-1,6-bisphosphate (FBP) and ADP. Ref.11

Catalytic activity

ATP + D-fructose 6-phosphate = ADP + D-fructose 1,6-bisphosphate. Ref.11

Cofactor

Magnesium.

Enzyme regulation

Allosteric enzyme activated by ADP, AMP, or fructose bisphosphate and inhibited by ATP or citrate. GlcNAcylation by OGT overcomes allosteric regulation. Ref.11

Pathway

Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-phosphate and glycerone phosphate from D-glucose: step 3/4. HAMAP-Rule MF_00339

Subunit structure

Tetramer. Muscle is M4, liver is L4, and red cell is M3L, M2L2, or ML3.

Post-translational modification

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. HAMAP-Rule MF_00339

Miscellaneous

In human PFK exists as a system of 3 types of subunits, PFKM (muscle), PFKL (liver) and PFKP (platelet) isoenzymes.

Glycosylation may play a role in cancer cell proliferation: inhibition of 6-phosphofructokinase activity and subsequent redirection of the glucose flux through the oxidative pentose phosphate pathway confers a selective growth advantage on cancer cells. Moreover GlcNAcylation is observed in multiple cancer cell lines and tissue samples and GlcNAcylation leads to larger xenografts tunors in mice (Ref.11).

Sequence similarities

Belongs to the phosphofructokinase family. Two domains subfamily.

Ontologies

Keywords
   Biological processGlycolysis
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainRepeat
   LigandATP-binding
Magnesium
Metal-binding
Nucleotide-binding
   Molecular functionKinase
Transferase
   PTMAcetylation
Glycoprotein
Phosphoprotein
   Technical termAllosteric enzyme
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processcarbohydrate metabolic process

Traceable author statement. Source: Reactome

carbohydrate phosphorylation

Inferred from direct assay Ref.11PubMed 6444532PubMed 6444721PubMed 8780720. Source: GOC

fructose 1,6-bisphosphate metabolic process

Inferred from direct assay Ref.11. Source: UniProtKB

fructose 6-phosphate metabolic process

Inferred from direct assay PubMed 6444532PubMed 6444721. Source: UniProtKB

glucose metabolic process

Traceable author statement. Source: Reactome

glycolysis

Inferred from direct assay Ref.11PubMed 6227635PubMed 6444532. Source: UniProtKB

negative regulation of insulin secretion

Inferred from electronic annotation. Source: Ensembl

protein homotetramerization

Inferred from electronic annotation. Source: Ensembl

protein oligomerization

Inferred from direct assay PubMed 6444721. Source: BHF-UCL

response to glucose

Inferred from direct assay Ref.11. Source: UniProtKB

small molecule metabolic process

Traceable author statement. Source: Reactome

   Cellular_component6-phosphofructokinase complex

Inferred from direct assay PubMed 6444532PubMed 6444721. Source: UniProtKB

cytosol

Inferred from direct assay PubMed 16780588. Source: UniProtKB

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867PubMed 19199708PubMed 20458337. Source: UniProt

   Molecular_function6-phosphofructokinase activity

Inferred from direct assay Ref.11PubMed 6444532PubMed 6444721PubMed 8780720. Source: UniProtKB

ATP binding

Inferred from direct assay PubMed 8780720. Source: UniProtKB

fructose binding

Inferred from direct assay PubMed 8780720. Source: BHF-UCL

fructose-6-phosphate binding

Inferred from direct assay PubMed 6444721. Source: BHF-UCL

identical protein binding

Inferred from physical interaction PubMed 6444721. Source: IntAct

kinase binding

Inferred from physical interaction PubMed 6444721. Source: BHF-UCL

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

itself2EBI-487243,EBI-487243
PFKMP082376EBI-487243,EBI-514788

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P17858-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P17858-2)

Also known as: a;

The sequence of this isoform differs from the canonical sequence as follows:
     1-28: MAAVDLEKLRASGAGKAIGVLTSGGDAQ → MCNQGRGRES...GGTSIMSRLG
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.5 Ref.6
Chain2 – 7807796-phosphofructokinase, liver type HAMAP-Rule MF_00339
PRO_0000112021

Regions

Nucleotide binding35 – 395ATP By similarity
Nucleotide binding193 – 1975ATP By similarity
Nucleotide binding210 – 22617ATP By similarity

Sites

Active site1661Proton acceptor By similarity
Metal binding2241Magnesium; via carbonyl oxygen By similarity
Binding site2011Substrate By similarity
Binding site2921Substrate By similarity
Binding site2981Substrate By similarity
Binding site3011Substrate By similarity

Amino acid modifications

Modified residue21N-acetylalanine Ref.6 Ref.9 Ref.10
Modified residue6401Phosphotyrosine By similarity
Modified residue7751Phosphoserine Ref.7
Glycosylation5291O-linked (GlcNAc) Ref.11

Natural variations

Alternative sequence1 – 2828MAAVD…GGDAQ → MCNQGRGRESSRGGLHVQGS CRGLSRSPQQETGFAKAPAG TDCFFHCSPGSRGQGDRKEE VTSEPGGTSIMSRLG in isoform 2.
VSP_011854
Natural variant811G → A. Ref.2
VAR_006070
Natural variant1511R → W. Ref.1
VAR_006071
Natural variant2371D → V.
Corresponds to variant rs1057037 [ dbSNP | Ensembl ].
VAR_030872

Experimental info

Mutagenesis5271T → A: Does not affect GlcNAcylation. Ref.11
Mutagenesis5291S → A: Prevents GlcNAcylation and enhance enzyme activity. Ref.11
Sequence conflict271A → R in CAA33597. Ref.1
Sequence conflict271A → R in CAB46744. Ref.2
Sequence conflict861S → T in CAB46744. Ref.2
Sequence conflict891C → S in CAA33597. Ref.1
Sequence conflict891C → S in CAB46744. Ref.2
Sequence conflict1031Y → N in CAB46744. Ref.2
Sequence conflict2361E → EAPPE in CAB46744. Ref.2
Sequence conflict3861K → R in CAB46744. Ref.2
Sequence conflict3891A → T in CAA33597. Ref.1
Sequence conflict3891A → T in CAB46744. Ref.2
Sequence conflict6481K → N in AAH08964. Ref.4
Sequence conflict6481K → N in AAH09919. Ref.4
Sequence conflict7171V → A in AAH08964. Ref.4
Sequence conflict7171V → A in AAH09919. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified March 6, 2007. Version 6.
Checksum: 0D686CE074E9626D

FASTA78085,018
        10         20         30         40         50         60 
MAAVDLEKLR ASGAGKAIGV LTSGGDAQGM NAAVRAVTRM GIYVGAKVFL IYEGYEGLVE 

        70         80         90        100        110        120 
GGENIKQANW LSVSNIIQLG GTIIGSARCK AFTTREGRRA AAYNLVQHGI TNLCVIGGDG 

       130        140        150        160        170        180 
SLTGANIFRS EWGSLLEELV AEGKISETTA RTYSHLNIAG LVGSIDNDFC GTDMTIGTDS 

       190        200        210        220        230        240 
ALHRIMEVID AITTTAQSHQ RTFVLEVMGR HCGYLALVSA LASGADWLFI PEAPPEDGWE 

       250        260        270        280        290        300 
NFMCERLGET RSRGSRLNII IIAEGAIDRN GKPISSSYVK DLVVQRLGFD TRVTVLGHVQ 

       310        320        330        340        350        360 
RGGTPSAFDR ILSSKMGMEA VMALLEATPD TPACVVTLSG NQSVRLPLME CVQMTKEVQK 

       370        380        390        400        410        420 
AMDDKRFDEA TQLRGGSFEN NWNIYKLLAH QKPPKEKSNF SLAILNVGAP AAGMNAAVRS 

       430        440        450        460        470        480 
AVRTGISHGH TVYVVHDGFE GLAKGQVQEV GWHDVAGWLG RGGSMLGTKR TLPKGQLESI 

       490        500        510        520        530        540 
VENIRIYGIH ALLVVGGFEA YEGVLQLVEA RGRYEELCIV MCVIPATISN NVPGTDFSLG 

       550        560        570        580        590        600 
SDTAVNAAME SCDRIKQSAS GTKRRVFIVE TMGGYCGYLA TVTGIAVGAD AAYVFEDPFN 

       610        620        630        640        650        660 
IHDLKVNVEH MTEKMKTDIQ RGLVLRNEKC HDYYTTEFLY NLYSSEGKGV FDCRTNVLGH 

       670        680        690        700        710        720 
LQQGGAPTPF DRNYGTKLGV KAMLWLSEKL REVYRKGRVF ANAPDSACVI GLKKKAVAFS 

       730        740        750        760        770        780 
PVTELKKDTD FEHRMPREQW WLSLRLMLKM LAQYRISMAA YVSGELEHVT RRTLSMDKGF 

« Hide

Isoform 2 (a) [UniParc].

Checksum: ADBECCB9B1FB234C
Show »

FASTA82790,203

References

« Hide 'large scale' references
[1]"The primary structure of human liver type phosphofructokinase and its comparison with other types of PFK."
Levanon D., Danciger E., Dafni N., Bernstein Y., Elson A., Moens W., Brandeis M., Groner Y.
DNA 8:733-743(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT TRP-151.
Tissue: Liver.
[2]"The structure of the human liver-type phosphofructokinase gene."
Elson A., Levanon D., Brandeis M., Dafni N., Bernstein Y., Danciger E., Groner Y.
Genomics 7:47-56(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), VARIANT ALA-81.
[3]"The DNA sequence of human chromosome 21."
Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S., Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M., Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A. expand/collapse author list , Menzel U., Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A., Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J., Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K., Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G., Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J., Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S., Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K., Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.
Nature 405:311-319(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Kidney, Lung and Muscle.
[5]"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides."
Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J.
Nat. Biotechnol. 21:566-569(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-10 (ISOFORM 1).
Tissue: Platelet.
[6]Bienvenut W.V., Gao M., Leug H., Pchelintsev N., Adams P.D.
Submitted (JUL-2009) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 2-10; 17-35 AND 185-210, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Prostatic carcinoma.
[7]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-775, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[8]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]"Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"Phosphofructokinase 1 glycosylation regulates cell growth and metabolism."
Yi W., Clark P.M., Mason D.E., Keenan M.C., Hill C., Goddard W.A. III, Peters E.C., Driggers E.M., Hsieh-Wilson L.C.
Science 337:975-980(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, ENZYME REGULATION, GLYCOSYLATION AT SER-529, MUTAGENESIS OF THR-527 AND SER-529.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X15573 mRNA. Translation: CAA33597.1.
X16911 expand/collapse EMBL AC list , X16912, X16913, X16914, X16915, X16916, X16917, X16918, X16919, X16920, X16921, X16922, X16923, X16924, X16925, X16926, X16927, X16928, X16929, X16930 Genomic DNA. Translation: CAB46744.1.
AP001754 Genomic DNA. Translation: BAA95561.1.
BC006422 mRNA. Translation: AAH06422.1.
BC007536 mRNA. Translation: AAH07536.1.
BC008964 mRNA. Translation: AAH08964.1.
BC009919 mRNA. Translation: AAH09919.1.
PIRA33639.
RefSeqNP_002617.3. NM_002626.4.
UniGeneHs.255093.

3D structure databases

ProteinModelPortalP17858.
SMRP17858. Positions 10-754.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111232. 29 interactions.
IntActP17858. 10 interactions.
MINTMINT-5004093.
STRING9606.ENSP00000269848.

Chemistry

BindingDBP17858.

PTM databases

PhosphoSiteP17858.

Polymorphism databases

DMDM134048493.

Proteomic databases

PaxDbP17858.
PRIDEP17858.

Protocols and materials databases

DNASU5211.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000349048; ENSP00000269848; ENSG00000141959. [P17858-1]
ENST00000403390; ENSP00000384038; ENSG00000141959. [P17858-2]
GeneID5211.
KEGGhsa:5211.
UCSCuc002zek.3. human. [P17858-2]
uc002zel.3. human. [P17858-1]

Organism-specific databases

CTD5211.
GeneCardsGC21P045719.
H-InvDBHIX0016166.
HGNCHGNC:8876. PFKL.
HPAHPA030047.
MIM171860. gene.
neXtProtNX_P17858.
PharmGKBPA33215.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0205.
HOGENOMHOG000200154.
HOVERGENHBG000976.
KOK00850.
OMAVQHGITN.
OrthoDBEOG7ZSHV5.
PhylomeDBP17858.
TreeFamTF300411.

Enzyme and pathway databases

BioCycMetaCyc:HS06881-MONOMER.
ReactomeREACT_111217. Metabolism.
SABIO-RKP17858.
UniPathwayUPA00109; UER00182.

Gene expression databases

ArrayExpressP17858.
BgeeP17858.
CleanExHS_PFKL.
GenevestigatorP17858.

Family and domain databases

HAMAPMF_00339. Phosphofructokinase.
InterProIPR009161. 6-phosphofructokinase_euk.
IPR022953. Phosphofructokinase.
IPR015912. Phosphofructokinase_CS.
IPR000023. Phosphofructokinase_dom.
[Graphical view]
PfamPF00365. PFK. 2 hits.
[Graphical view]
PIRSFPIRSF000533. ATP_PFK_euk. 1 hit.
PRINTSPR00476. PHFRCTKINASE.
SUPFAMSSF53784. SSF53784. 2 hits.
TIGRFAMsTIGR02478. 6PF1K_euk. 1 hit.
PROSITEPS00433. PHOSPHOFRUCTOKINASE. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPFKL. human.
GeneWikiPFKL.
GenomeRNAi5211.
NextBio20154.
PMAP-CutDBP17858.
PROP17858.
SOURCESearch...

Entry information

Entry nameK6PL_HUMAN
AccessionPrimary (citable) accession number: P17858
Secondary accession number(s): Q96A64, Q96IH4, Q9BR91
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: March 6, 2007
Last modified: April 16, 2014
This is version 170 of the entry and version 6 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 21

Human chromosome 21: entries, gene names and cross-references to MIM