Reviewed, UniProtKB/Swiss-Prot O60825 (F262_HUMAN)

Names and origin

Protein names

Recommended name:
    6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2
Alternative name(s):
    PFK-2/FBPase-2
    6PF-2-K/Fru-2,6-P2ASE heart-type isozyme
Including the following 2 domains:
    1- Recommended name:
            6-phosphofructo-2-kinase
              EC=2.7.1.105
    2- Recommended name:
            Fructose-2,6-bisphosphatase
              EC=3.1.3.46

Gene names

Name:

PFKFB2

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	505 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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 the activation of the kinase activity.
Subunit structure	Homodimer By similarity.
Tissue specificity	Heart.
Sequence similarities	In the C-terminal section; belongs to the phosphoglycerate mutase family.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Nucleotide-binding
Molecular function	Hydrolase Kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Multifunctional enzyme
Gene Ontology (GO)
Biological process	fructose 2,6-bisphosphate metabolic process Inferred from electronic annotation. Source: InterPro
Cellular component	cytosol Inferred from Experiment. Source: Reactome
Molecular function	6-phosphofructo-2-kinase activity Ref.1 Inferred from Experiment. Source: Reactome ATP binding Inferred from electronic annotation. Source: UniProtKB-KW fructose-2,6-bisphosphate 2-phosphatase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O60825-1)

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: O60825-2)

The sequence of this isoform differs from the canonical sequence as follows:
     451-505: NNFPKNQTPV...RAQDMQEGAD → AAETTLAVRRRPSAASLMLPC

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 505	505	6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2		PRO_0000179964
Regions
	Nucleotide binding	45 – 52	8	ATP Potential
	Region	1 – 248	248	6-phosphofructo-2-kinase
	Region	249 – 505	257	Fructose-2,6-bisphosphatase
Sites
	Active site	128	1	Potential
	Active site	158	1	Potential
	Active site	257	1	Tele-phosphohistidine intermediate By similarity
	Active site	326	1	Potential
	Active site	391	1	Proton donor By similarity
	Binding site	102	1	Fructose-6-phosphate By similarity
	Binding site	193	1	Fructose-6-phosphate By similarity
Amino acid modifications
	Modified residue	29	1	Phosphoserine; by PKA By similarity
	Modified residue	466	1	Phosphoserine Ref.6 Ref.7
	Modified residue	468	1	Phosphothreonine Ref.7
	Modified residue	475	1	Phosphothreonine; by PKC By similarity
	Modified residue	483	1	Phosphoserine Ref.7
	Modified residue	493	1	Phosphoserine Ref.7
Natural variations
	Alternative sequence	451 – 505	55	NNFPK…QEGAD → AAETTLAVRRRPSAASLMLP C in isoform 2.		VSP_004675
Experimental info
	Sequence conflict	28	1	Missing in CAA06605. Ref.1
	Sequence conflict	303 – 304	2	QL → HV in CAA06606. Ref.1
	Sequence conflict	372	1	R → L in CAA06606. Ref.1
	Sequence conflict	396	1	R → H in CAA06606. Ref.1
	Sequence conflict	406	1	G → D in CAA06606. Ref.1
	Sequence conflict	427	1	A → T in CAA06606. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 24, 2001. Version 2. Checksum: 5CD6A933A7EBF604	FASTA	505	58,477
	10 20 30 40 50 60 MSGASSSEQN NNSYETKTPN LRMSEKKCSW ASYMTNSPTL IVMIGLPARG KTYVSKKLTR 70 80 90 100 110 120 YLNWIGVPTK VFNLGVYRRE AVKSYKSYDF FRHDNEEAMK IRKQCALVAL EDVKAYLTEE 130 140 150 160 170 180 NGQIAVFDAT NTTRERRDMI LNFAEQNSFK VFFVESVCDD PDVIAANILE VKVSSPDYPE 190 200 210 220 230 240 RNRENVMEDF LKRIECYKVT YRPLDPDNYD KDLSFIKVIN VGQRFLVNRV QDYIQSKIVY 250 260 270 280 290 300 YLMNIHVQPR TIYLCRHGES EFNLLGKIGG DSGLSVRGKQ FAQALRKFLE EQEITDLKVW 310 320 330 340 350 360 TSQLKRTIQT AESLGVPYEQ WKILNEIDAG VCEEMTYAEI EKRYPEEFAL RDQEKYLYRY 370 380 390 400 410 420 PGGESYQDLV QRLEPVIMEL ERQGNVLVIS HQAVMRCLLA YFLDKGADEL PYLRCPLHTI 430 440 450 460 470 480 FKLTPVAYGC KVETIKLNVE AVNTHRDKPT NNFPKNQTPV RMRRNSFTPL SSSNTIRRPR 490 500 NYSVGSRPLK PLSPLRAQDM QEGAD
	Isoform 2. Checksum: 2B9C8957889F4D61	FASTA	471	54,406
	10 20 30 40 50 60 MSGASSSEQN NNSYETKTPN LRMSEKKCSW ASYMTNSPTL IVMIGLPARG KTYVSKKLTR 70 80 90 100 110 120 YLNWIGVPTK VFNLGVYRRE AVKSYKSYDF FRHDNEEAMK IRKQCALVAL EDVKAYLTEE 130 140 150 160 170 180 NGQIAVFDAT NTTRERRDMI LNFAEQNSFK VFFVESVCDD PDVIAANILE VKVSSPDYPE 190 200 210 220 230 240 RNRENVMEDF LKRIECYKVT YRPLDPDNYD KDLSFIKVIN VGQRFLVNRV QDYIQSKIVY 250 260 270 280 290 300 YLMNIHVQPR TIYLCRHGES EFNLLGKIGG DSGLSVRGKQ FAQALRKFLE EQEITDLKVW 310 320 330 340 350 360 TSQLKRTIQT AESLGVPYEQ WKILNEIDAG VCEEMTYAEI EKRYPEEFAL RDQEKYLYRY 370 380 390 400 410 420 PGGESYQDLV QRLEPVIMEL ERQGNVLVIS HQAVMRCLLA YFLDKGADEL PYLRCPLHTI 430 440 450 460 470 FKLTPVAYGC KVETIKLNVE AVNTHRDKPT AAETTLAVRR RPSAASLMLP C

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sequence and structure of the human 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase heart isoform gene (PFKFB2)." Heine-Suner D., Diaz-Guillen M.A., Lange A.J., Rodriguez de Cordoba S. Eur. J. Biochem. 254:103-110(1998) [PubMed: 9652401] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
[2]	"Isolation of novel heart-specific genes using the BodyMap database." Soejima H., Kawamoto S., Akai J., Miyoshi O., Arai Y., Morohka T., Matsuo S., Niikawa N., Kimura A., Okubo K., Mukai T. Genomics 74:115-120(2001) [PubMed: 11374908] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Heart.
[3]	"Human insulinoma PFK2/F26DPase." Matsutani A. Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[4]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[6]	"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra." Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D. J. Proteome Res. 6:4150-4162(2007) [PubMed: 17924679] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-466, MASS SPECTROMETRY. Tissue: Epithelium.
[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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-466; THR-468; SER-483 AND SER-493, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AJ005577 Genomic DNA. Translation: CAA06605.1. AJ005578 mRNA. Translation: CAA06606.1. AB044805 mRNA. Translation: BAB19681.1. AF470623 mRNA. Translation: AAL99386.1. AL445493 Genomic DNA. Translation: CAH70777.1. BC069350 mRNA. Translation: AAH69350.1. BC069385 mRNA. Translation: AAH69385.1. BC069583 mRNA. Translation: AAH69583.1. BC069586 mRNA. Translation: AAH69586.1. BC069600 mRNA. Translation: AAH69600.1. BC075075 mRNA. Translation: AAH75075.1. BC075076 mRNA. Translation: AAH75076.1. BC112103 mRNA. Translation: AAI12104.1. BC112105 mRNA. Translation: AAI12106.1.
IPI	IPI00220808. IPI00305589.
RefSeq	NP_001018063.1. NP_006203.2.
UniGene	Hs.282702
3D structure databases
HSSP	HSSP built from PDB template 1C80 based on UniProtKB P07953.
SMR	O60825. Positions 38-451.
ModBase	Search...
Protein-protein interaction databases
IntAct	O60825. 2 interactions.
PTM databases
PhosphoSite	O60825.
Proteomic databases
PRIDE	O60825.
Genome annotation databases
Ensembl	ENSG00000123836. Homo sapiens. [Contig view]
GeneID	5208.
KEGG	hsa:5208.
UCSC	uc001hfg.1. human.
Organism-specific databases
GeneCards	GC01P205293.
H-InvDB	HIX0023719.
HGNC	HGNC:8873. PFKFB2.
MIM	171835. gene.
PharmGKB	PA33212.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	O60825.
HOVERGEN	O60825.
OMA	O60825. HPRTIYL.
Enzyme and pathway databases
BRENDA	2.7.1.105. 247. 3.1.3.46. 247.
Reactome	REACT_1505. Integration of energy metabolism. REACT_15380. Diabetes pathways. REACT_474. Metabolism of carbohydrates.
Gene expression databases
ArrayExpress	O60825.
Bgee	O60825.
CleanEx	HS_PFKFB2.
GermOnline	ENSG00000123836. Homo sapiens.
Family and domain databases
InterPro	IPR003094. 6Pfruct_kin. IPR013079. 6Phosfructo_kin. IPR016260. Bifunct_6PFK/fruc_bisP_Ptase. IPR001345. PG/BPGM_mutase. IPR013078. PG_mutase. [Graphical view]
PANTHER	PTHR10606. 6Pfruct_kin. 1 hit.
Pfam	PF01591. 6PF2K. 1 hit. PF00300. PGAM. 1 hit. [Graphical view]
PIRSF	PIRSF000709. 6PFK_2-Ptase. 1 hit.
PRINTS	PR00991. 6PFRUCTKNASE.
PROSITE	PS00175. PG_MUTASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	20140.
SOURCE	Search...

Entry information

Entry name

F262_HUMAN

Accession

Primary (citable) accession number: O60825
Secondary accession number(s): O60824, Q5VVQ4, Q9H3P1

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 24, 2001
Last sequence update:	January 24, 2001
Last modified:	July 7, 2009
This is version 91 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)