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P16118 (F261_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 154. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 1

Short name=6PF-2-K/Fru-2,6-P2ase 1
Short name=PFK/FBPase 1
Alternative name(s):
6PF-2-K/Fru-2,6-P2ase liver isozyme

Including the following 2 domains:

  1. 6-phosphofructo-2-kinase
    EC=2.7.1.105
  2. Fructose-2,6-bisphosphatase
    EC=3.1.3.46
Gene names
Name:PFKFB1
Synonyms:F6PK, PFRX
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length471 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Synthesis and degradation of fructose 2,6-bisphosphate.

Catalytic activity

Beta-D-fructose 2,6-bisphosphate + H2O = D-fructose 6-phosphate + phosphate.

ATP + D-fructose 6-phosphate = ADP + beta-D-fructose 2,6-bisphosphate.

Enzyme regulation

Phosphorylation results in inhibition of the kinase activity.

Subunit structure

Homodimer. Ref.6

Tissue specificity

Liver.

Sequence similarities

In the C-terminal section; belongs to the phosphoglycerate mutase family.

Ontologies

Keywords
   LigandATP-binding
Nucleotide-binding
   Molecular functionHydrolase
Kinase
Transferase
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Multifunctional enzyme
Reference proteome
Gene Ontology (GO)
   Biological_processcarbohydrate metabolic process

Traceable author statement. Source: Reactome

dephosphorylation

Inferred from direct assay Ref.5. Source: GOC

energy reserve metabolic process

Traceable author statement. Source: Reactome

fructose 2,6-bisphosphate metabolic process

Inferred from direct assay Ref.5. Source: UniProtKB

fructose metabolic process

Inferred from electronic annotation. Source: InterPro

gluconeogenesis

Traceable author statement Ref.6. Source: UniProtKB

glucose metabolic process

Traceable author statement. Source: Reactome

glycolysis

Traceable author statement Ref.6. Source: UniProtKB

intracellular signal transduction

Traceable author statement. Source: Reactome

organ regeneration

Inferred from electronic annotation. Source: Ensembl

positive regulation of glucokinase activity

Inferred from electronic annotation. Source: Ensembl

response to cAMP

Inferred from electronic annotation. Source: Ensembl

response to glucagon

Inferred from electronic annotation. Source: Ensembl

response to glucocorticoid

Inferred from electronic annotation. Source: Ensembl

response to insulin

Inferred from electronic annotation. Source: Ensembl

response to starvation

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

   Cellular_component6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 1 complex

Inferred from direct assay Ref.6. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

   Molecular_function6-phosphofructo-2-kinase activity

Traceable author statement Ref.6. Source: UniProtKB

ATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

fructose-2,6-bisphosphate 2-phosphatase activity

Inferred from direct assay Ref.5. Source: UniProtKB

fructose-6-phosphate binding

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

GCKP355572EBI-709807,EBI-709928

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 4714706-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 1
PRO_0000179960

Regions

Nucleotide binding49 – 579ATP
Nucleotide binding170 – 1756ATP
Nucleotide binding350 – 3534ATP By similarity
Nucleotide binding394 – 3985ATP By similarity
Region2 – 2502496-phosphofructo-2-kinase
Region251 – 471221Fructose-2,6-bisphosphatase

Sites

Active site1311 Potential
Active site1611 Potential
Active site2591Tele-phosphohistidine intermediate By similarity
Active site3281Proton donor/acceptor By similarity
Active site3931Proton donor/acceptor By similarity
Binding site821Fructose 6-phosphate By similarity
Binding site1051Fructose 6-phosphate By similarity
Binding site1331Fructose 6-phosphate By similarity
Binding site1391Fructose 6-phosphate By similarity
Binding site1751Fructose 6-phosphate By similarity
Binding site1961Fructose 6-phosphate By similarity
Binding site2001Fructose 6-phosphate By similarity
Binding site2581Fructose 2,6-bisphosphate
Binding site2651Fructose 2,6-bisphosphate
Binding site2711Fructose 2,6-bisphosphate; via amide nitrogen By similarity
Binding site3081Fructose 2,6-bisphosphate
Binding site3391Fructose 2,6-bisphosphate
Binding site3531Fructose 2,6-bisphosphate
Binding site3571Fructose 2,6-bisphosphate
Binding site3681Fructose 2,6-bisphosphate
Binding site3941Fructose 2,6-bisphosphate By similarity
Binding site3981Fructose 2,6-bisphosphate
Binding site4301ATP

Amino acid modifications

Modified residue21N-acetylserine By similarity
Modified residue331Phosphoserine; by PKA By similarity

Experimental info

Sequence conflict3051H → R in CAA36861. Ref.1
Sequence conflict3591R → H in AAA35818. Ref.5
Sequence conflict397 – 3982MR → HA in AAA35818. Ref.5

Secondary structure

................................................................. 471
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P16118 [UniParc].

Last modified November 1, 1997. Version 3.
Checksum: C4FF081A295FB7D3

FASTA47154,681
        10         20         30         40         50         60 
MSPEMGELTQ TRLQKIWIPH SSGSSRLQRR RGSSIPQFTN SPTMVIMVGL PARGKTYIST 

        70         80         90        100        110        120 
KLTRYLNWIG TPTKVFNLGQ YRREAVSYKN YEFFLPDNME ALQIRKQCAL AALKDVHNYL 

       130        140        150        160        170        180 
SHEEGHVAVF DATNTTRERR SLILQFAKEH GYKVFFIESI CNDPGIIAEN IRQVKLGSPD 

       190        200        210        220        230        240 
YIDCDREKVL EDFLKRIECY EVNYQPLDEE LDSHLSYIKI FDVGTRYMVN RVQDHIQSRT 

       250        260        270        280        290        300 
VYYLMNIHVT PRSIYLCRHG ESELNIRGRI GGDSGLSVRG KQYAYALANF IQSQGISSLK 

       310        320        330        340        350        360 
VWTSHMKRTI QTAEALGVPY EQWKALNEID AGVCEEMTYE EIQEHYPEEF ALRDQDKYRY 

       370        380        390        400        410        420 
RYPKGESYED LVQRLEPVIM ELERQENVLV ICHQAVMRCL LAYFLDKSSD ELPYLKCPLH 

       430        440        450        460        470 
TVLKLTPVAY GCKVESIYLN VEAVNTHREK PENVDITREP EEALDTVPAH Y 

« Hide

References

« Hide 'large scale' references
[1]"Sequence of human liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase."
Lange A.J., Pilkis S.J.
Nucleic Acids Res. 18:3652-3652(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Liver.
[3]"The DNA sequence of the human X chromosome."
Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. expand/collapse author list , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R.
Nature 434:325-337(2005) [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].
[5]"Molecular cloning, sequence analysis, and expression of a human liver cDNA coding for fructose-6-P,2-kinase:fructose-2,6-bisphosphatase."
Algaier J., Uyeda K.
Biochem. Biophys. Res. Commun. 153:328-333(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 94-471.
Tissue: Liver.
[6]"Tissue-specific structure/function differentiation of the liver isoform of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase."
Lee Y.H., Li Y., Uyeda K., Hasemann C.A.
J. Biol. Chem. 278:523-530(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 40-471 IN COMPLEX WITH ATP ANALOG, SUBUNIT.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X52638 mRNA. Translation: CAA36861.1.
AK314089 mRNA. Translation: BAG36785.1.
AL049732, AL020991 Genomic DNA. Translation: CAI42048.1.
AL020991, AL049732 Genomic DNA. Translation: CAI43127.1.
BC096079 mRNA. Translation: AAH96079.1.
M19938 mRNA. Translation: AAA35818.1.
PIRS12732.
RefSeqNP_001258733.1. NM_001271804.1.
NP_002616.2. NM_002625.3.
UniGeneHs.444304.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1K6MX-ray2.40A/B40-471[»]
ProteinModelPortalP16118.
SMRP16118. Positions 7-471.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111228. 6 interactions.
IntActP16118. 3 interactions.
MINTMINT-6772805.
STRING9606.ENSP00000364145.

PTM databases

PhosphoSiteP16118.

Polymorphism databases

DMDM2507178.

Proteomic databases

PaxDbP16118.
PRIDEP16118.

Protocols and materials databases

DNASU5207.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000375006; ENSP00000364145; ENSG00000158571.
GeneID5207.
KEGGhsa:5207.
UCSCuc004dty.2. human.

Organism-specific databases

CTD5207.
GeneCardsGC0XM054976.
HGNCHGNC:8872. PFKFB1.
HPAHPA013959.
MIM311790. gene.
neXtProtNX_P16118.
PharmGKBPA33211.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0406.
HOGENOMHOG000181112.
HOVERGENHBG005628.
InParanoidP16118.
KOK01103.
OMANIRGRIG.
OrthoDBEOG7M3J03.
PhylomeDBP16118.
TreeFamTF313541.

Enzyme and pathway databases

BRENDA3.1.3.46. 2681.
ReactomeREACT_111217. Metabolism.
SABIO-RKP16118.

Gene expression databases

ArrayExpressP16118.
BgeeP16118.
CleanExHS_PFKFB1.
GenevestigatorP16118.

Family and domain databases

Gene3D3.40.50.300. 1 hit.
InterProIPR003094. 6Pfruct_kin.
IPR013079. 6Phosfructo_kin.
IPR016260. Bifunct_6PFK/fruc_bisP_Ptase.
IPR013078. His_Pase_superF_clade-1.
IPR027417. P-loop_NTPase.
IPR001345. PG/BPGM_mutase_AS.
[Graphical view]
PANTHERPTHR10606. PTHR10606. 1 hit.
PfamPF01591. 6PF2K. 1 hit.
PF00300. His_Phos_1. 1 hit.
[Graphical view]
PIRSFPIRSF000709. 6PFK_2-Ptase. 1 hit.
PRINTSPR00991. 6PFRUCTKNASE.
SMARTSM00855. PGAM. 1 hit.
[Graphical view]
SUPFAMSSF52540. SSF52540. 1 hit.
PROSITEPS00175. PG_MUTASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP16118.
GenomeRNAi5207.
NextBio20136.
PROP16118.
SOURCESearch...

Entry information

Entry nameF261_HUMAN
AccessionPrimary (citable) accession number: P16118
Secondary accession number(s): B2RA88, Q5JXS5, Q99951
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: November 1, 1997
Last modified: April 16, 2014
This is version 154 of the entry and version 3 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

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

Human chromosome X

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