O60825 (F262_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2
Short name=6PF-2-K/Fru-2,6-P2ase 2
Short name=PFK/FBPase 2

Alternative name(s):
6PF-2-K/Fru-2,6-P2ase heart-type 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:

PFKFB2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	505 AA.
Sequence status	Complete.
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.
Post-translational modification	Phosphorylation by AMPK stimulates activity.
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 Reference proteome
Gene Ontology (GO)
Biological_process	fructose 2,6-bisphosphate metabolic process Inferred from electronic annotation. Source: InterPro fructose metabolic process Traceable author statement Ref.1. Source: ProtInc glycolysis Inferred from direct assay Ref.8. Source: UniProtKB lactate metabolic process Inferred from electronic annotation. Source: Compara positive regulation of glucokinase activity Inferred from electronic annotation. Source: Compara positive regulation of insulin secretion Inferred from electronic annotation. Source: Compara pyruvate metabolic process Inferred from electronic annotation. Source: Compara response to glucose stimulus Inferred from electronic annotation. Source: Compara small molecule metabolic process Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome
Molecular_function	6-phosphofructo-2-kinase activity Inferred from direct assay Ref.8. Source: UniProtKB 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-bisphosphatase 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; by AMPK Ref.8 Ref.9 Ref.11 Ref.12
	Modified residue	468	1	Phosphothreonine Ref.9
	Modified residue	475	1	Phosphothreonine; by PKC By similarity
	Modified residue	483	1	Phosphoserine Ref.9 Ref.11
	Modified residue	493	1	Phosphoserine Ref.9 Ref.11
Natural variations
	Alternative sequence	451 – 505	55	NNFPK…QEGAD → AAETTLAVRRRPSAASLMLP C in isoform 2.		VSP_004675
Experimental info
	Mutagenesis	466	1	S → E: Constitutively active mutant that cannot be phosphorylated and further activated by AMPK. Ref.8
	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 [UniParc]. 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] [Europe PMC] [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] [Europe PMC] [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]	"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. , 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] (ISOFORM 2). Tissue: Trachea.
[5]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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] (ISOFORM 1). Tissue: Brain.
[8]	"Phosphorylation and activation of heart PFK-2 by AMPK has a role in the stimulation of glycolysis during ischaemia." Marsin A.S., Bertrand L., Rider M.H., Deprez J., Beauloye C., Vincent M.F., Van den Berghe G., Carling D., Hue L. Curr. Biol. 10:1247-1255(2000) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-466, MUTAGENESIS OF SER-466.
[9]	"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-466; THR-468; SER-483 AND SER-493, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Leukemic T-cell.
[11]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-466; SER-483 AND SER-493, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[12]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-466, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ005577 Genomic DNA. Translation: CAA06605.1. AJ005578 mRNA. Translation: CAA06606.1. AB044805 mRNA. Translation: BAB19681.1. AF470623 mRNA. Translation: AAL99386.1. AK292883 mRNA. Translation: BAF85572.1. AL445493 Genomic DNA. Translation: CAH70777.1. AL445493 Genomic DNA. Translation: CAH70778.1. CH471100 Genomic DNA. Translation: EAW93508.1. 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. NM_001018053.1. NP_006203.2. NM_006212.2.
UniGene	Hs.282702.
3D structure databases
ProteinModelPortal	O60825.
ModBase	Search...
Protein-protein interaction databases
IntAct	O60825. 2 interactions.
MINT	MINT-3000455.
STRING	9606.ENSP00000356047.
PTM databases
PhosphoSite	O60825.
Proteomic databases
PaxDb	O60825.
PRIDE	O60825.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000367079; ENSP00000356046; ENSG00000123836. ENST00000367080; ENSP00000356047; ENSG00000123836.
GeneID	5208.
KEGG	hsa:5208.
UCSC	uc001hfg.3. human.
Organism-specific databases
CTD	5208.
GeneCards	GC01P207226.
HGNC	HGNC:8873. PFKFB2.
MIM	171835. gene.
neXtProt	NX_O60825.
PharmGKB	PA33212.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0406.
HOGENOM	HOG000181112.
HOVERGEN	HBG005628.
InParanoid	O60825.
KO	K01103.
OMA	ALDMQEG.
OrthoDB	EOG408N7S.
PhylomeDB	O60825.
Enzyme and pathway databases
BRENDA	3.1.3.46. 2681.
Reactome	REACT_111217. Metabolism.
SABIO-RK	O60825.
Gene expression databases
ArrayExpress	O60825.
Bgee	O60825.
CleanEx	HS_PFKFB2.
Genevestigator	O60825.
GermOnline	ENSG00000123836. Homo sapiens.
Family and domain databases
InterPro	IPR003094. 6Pfruct_kin. IPR013079. 6Phosfructo_kin. IPR016260. Bifunct_6PFK/fruc_bisP_Ptase. IPR013078. His_Pase_superF_clade-1. IPR001345. PG/BPGM_mutase_AS. [Graphical view]
PANTHER	PTHR10606. PTHR10606. 1 hit.
Pfam	PF01591. 6PF2K. 1 hit. PF00300. His_Phos_1. 1 hit. [Graphical view]
PIRSF	PIRSF000709. 6PFK_2-Ptase. 1 hit.
PRINTS	PR00991. 6PFRUCTKNASE.
SMART	SM00855. PGAM. 1 hit. [Graphical view]
PROSITE	PS00175. PG_MUTASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	PFKFB2. human.
GenomeRNAi	5208.
NextBio	20140.
SOURCE	Search...

Entry information

Entry name

F262_HUMAN

Accession

Primary (citable) accession number: O60825
Secondary accession number(s): O60824 , Q5VVQ3, Q5VVQ4, Q9H3P1

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 24, 2001
Last sequence update:	January 24, 2001
Last modified:	May 1, 2013
This is version 129 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.