Q16875 (F263_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3
Short name=6PF-2-K/Fru-2,6-P2ase 3
Short name=PFK/FBPase 3

Alternative name(s):
6PF-2-K/Fru-2,6-P2ase brain/placenta-type isozyme
Renal carcinoma antigen NY-REN-56
iPFK-2

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:

PFKFB3

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	520 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.
Tissue specificity	Ubiquitous.
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	3D-structure Complete proteome Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Biological_process	fructose 2,6-bisphosphate metabolic process Non-traceable author statement. Source: UniProtKB fructose metabolic process Inferred from electronic annotation. Source: InterPro glycolysis Traceable author statement. Source: Reactome small molecule metabolic process Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome
Molecular_function	6-phosphofructo-2-kinase activity Non-traceable author statement Ref.1. 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: Q16875-1)

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: Q16875-2)

The sequence of this isoform differs from the canonical sequence as follows:
     506-520: NMKGSRSSADSSRKH → PLLGQACLT

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 520

520

6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3

PRO_0000179968

Regions

Nucleotide binding

42 – 49

8

ATP By similarity

Region

1 – 245

245

6-phosphofructo-2-kinase

Region

246 – 520

275

Fructose-2,6-bisphosphatase

Sites

Active site

125

1

Potential

Active site

155

1

Potential

Active site

254

1

Tele-phosphohistidine intermediate By similarity

Active site

323

1

Potential

Active site

388

1

Proton donor By similarity

Binding site

99

1

Fructose-6-phosphate By similarity

Binding site

190

1

Fructose-6-phosphate By similarity

Amino acid modifications

Modified residue

461

1

Phosphoserine; by AMPK Ref.8 Ref.9 Ref.10 Ref.11

Modified residue

463

1

Phosphothreonine Ref.9

Modified residue

467

1

Phosphoserine Ref.9 Ref.10 Ref.11

Modified residue

471

1

Phosphothreonine; by PKC By similarity

Natural variations

Alternative sequence

506 – 520

15

NMKGS…SSRKH → PLLGQACLT in isoform 2.

VSP_004680

Experimental info

Sequence conflict

136

1

M → V in AAB99795. Ref.3

Sequence conflict

141

1

A → G in AAC62000. Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

520

Helix Strand Turn

Details...

Beta strand

5 – 7

3

Turn

9 – 11

3

Beta strand

14 – 16

3

Beta strand

36 – 41

6

Beta strand

44 – 47

4

Helix

48 – 61

14

Beta strand

66 – 70

5

Helix

71 – 79

9

Helix

85 – 88

4

Helix

93 – 116

24

Beta strand

121 – 126

6

Helix

131 – 143

13

Beta strand

147 – 154

8

Helix

158 – 168

11

Turn

169 – 171

3

Helix

173 – 175

3

Helix

180 – 195

16

Turn

203 – 209

7

Beta strand

210 – 216

7

Turn

217 – 220

4

Beta strand

221 – 225

5

Helix

230 – 239

10

Beta strand

249 – 253

5

Helix

258 – 262

5

Helix

273 – 289

17

Beta strand

295 – 298

4

Helix

302 – 309

8

Turn

310 – 312

3

Beta strand

315 – 317

3

Helix

319 – 321

3

Helix

327 – 329

3

Helix

334 – 340

7

Helix

342 – 350

9

Turn

352 – 354

3

Helix

363 – 379

17

Beta strand

381 – 387

7

Helix

389 – 399

11

Turn

404 – 406

3

Helix

407 – 409

3

Beta strand

416 – 423

8

Beta strand

426 – 433

8

Helix

442 – 446

5

Helix

455 – 457

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: A7675A4ADC376879	FASTA	520	59,609
	10 20 30 40 50 60 MPLELTQSRV QKIWVPVDHR PSLPRSCGPK LTNSPTVIVM VGLPARGKTY ISKKLTRYLN 70 80 90 100 110 120 WIGVPTKVFN VGEYRREAVK QYSSYNFFRP DNEEAMKVRK QCALAALRDV KSYLAKEGGQ 130 140 150 160 170 180 IAVFDATNTT RERRHMILHF AKENDFKAFF IESVCDDPTV VASNIMEVKI SSPDYKDCNS 190 200 210 220 230 240 AEAMDDFMKR ISCYEASYQP LDPDKCDRDL SLIKVIDVGR RFLVNRVQDH IQSRIVYYLM 250 260 270 280 290 300 NIHVQPRTIY LCRHGENEHN LQGRIGGDSG LSSRGKKFAS ALSKFVEEQN LKDLRVWTSQ 310 320 330 340 350 360 LKSTIQTAEA LRLPYEQWKA LNEIDAGVCE ELTYEEIRDT YPEEYALREQ DKYYYRYPTG 370 380 390 400 410 420 ESYQDLVQRL EPVIMELERQ ENVLVICHQA VLRCLLAYFL DKSAEEMPYL KCPLHTVLKL 430 440 450 460 470 480 TPVAYGCRVE SIYLNVESVC THRERSEDAK KGPNPLMRRN SVTPLASPEP TKKPRINSFE 490 500 510 520 EHVASTSAAL PSCLPPEVPT QLPGQNMKGS RSSADSSRKH
	Isoform 2 [UniParc]. Checksum: 18FD1D267306853D	FASTA	514	58,876
	10 20 30 40 50 60 MPLELTQSRV QKIWVPVDHR PSLPRSCGPK LTNSPTVIVM VGLPARGKTY ISKKLTRYLN 70 80 90 100 110 120 WIGVPTKVFN VGEYRREAVK QYSSYNFFRP DNEEAMKVRK QCALAALRDV KSYLAKEGGQ 130 140 150 160 170 180 IAVFDATNTT RERRHMILHF AKENDFKAFF IESVCDDPTV VASNIMEVKI SSPDYKDCNS 190 200 210 220 230 240 AEAMDDFMKR ISCYEASYQP LDPDKCDRDL SLIKVIDVGR RFLVNRVQDH IQSRIVYYLM 250 260 270 280 290 300 NIHVQPRTIY LCRHGENEHN LQGRIGGDSG LSSRGKKFAS ALSKFVEEQN LKDLRVWTSQ 310 320 330 340 350 360 LKSTIQTAEA LRLPYEQWKA LNEIDAGVCE ELTYEEIRDT YPEEYALREQ DKYYYRYPTG 370 380 390 400 410 420 ESYQDLVQRL EPVIMELERQ ENVLVICHQA VLRCLLAYFL DKSAEEMPYL KCPLHTVLKL 430 440 450 460 470 480 TPVAYGCRVE SIYLNVESVC THRERSEDAK KGPNPLMRRN SVTPLASPEP TKKPRINSFE 490 500 510 EHVASTSAAL PSCLPPEVPT QLPGQPLLGQ ACLT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of cDNA encoding for a novel isozyme of fructose 6-phosphate, 2-kinase/fructose 2,6-bisphosphatase from human placenta." Sakai A., Kato M., Fukasawa M., Ishiguro M., Furuya E., Sakakibara R. J. Biochem. 119:506-511(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Placenta.
[2]	"Molecular cloning, expression, and chromosomal localization of a ubiquitously expressed human 6-phosphofructo-2-kinase/ fructose-2, 6-bisphosphatase gene (PFKFB3)." Manzano A., Rosa J.L., Ventura F., Perez J.X., Nadal M., Estivill X., Ambrosio S., Gil J., Bartrons R. Cytogenet. Cell Genet. 83:214-217(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Brain.
[3]	"Human brain 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase." El-Maghrabi M.R. Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1). Tissue: Brain.
[4]	"An inducible gene product for 6-phosphofructo-2-kinase with an AU-rich instability element: role in tumor cell glycolysis and the Warburg effect." Chesney J., Mitchell R.A., Benigni F., Bacher M., Spiegel L., Al-Abed Y., Han J.H., Metz C., Bucala R. Proc. Natl. Acad. Sci. U.S.A. 96:3047-3052(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Skeletal muscle.
[5]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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: Testis.
[7]	"Antigens recognized by autologous antibody in patients with renal-cell carcinoma." Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H., Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T., Old L.J. Int. J. Cancer 83:456-464(1999) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION AS A RENAL CANCER ANTIGEN. Tissue: Renal cell carcinoma.
[8]	"The stimulation of glycolysis by hypoxia in activated monocytes is mediated by AMP-activated protein kinase and inducible 6-phosphofructo-2-kinase." Marsin A.S., Bouzin C., Bertrand L., Hue L. J. Biol. Chem. 277:30778-30783(2002) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-461.
[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-461; THR-463 AND SER-467, 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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-461 AND SER-467, MASS SPECTROMETRY. 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-461 AND SER-467, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D49817 mRNA. Translation: BAA08624.1.
AF109735 mRNA. Translation: AAD08818.1.
AF041831 , AF041823, AF041824, AF041825, AF041826, AF041827, AF041828, AF041829, AF041830 Genomic DNA. Translation: AAB99795.1.
AF056320 mRNA. Translation: AAC62000.1.
AL359960, AL157395 Genomic DNA. Translation: CAH72163.1.
AL157395, AL359960 Genomic DNA. Translation: CAH73606.1.
BC040482 mRNA. Translation: AAH40482.1.

IPI

IPI00004511.
IPI00216306.

PIR

JC4626.

RefSeq

NP_001138915.1. NM_001145443.1.
NP_004557.1. NM_004566.3.

UniGene

Hs.195471.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2AXN	X-ray	2.10	A	1-520	[»]
2DWO	X-ray	2.25	A	1-520	[»]
2DWP	X-ray	2.70	A	1-520	[»]
2I1V	X-ray	2.50	B	1-520	[»]
3QPU	X-ray	2.30	A	1-520	[»]
3QPV	X-ray	2.50	A	1-520	[»]
3QPW	X-ray	2.25	A	1-520	[»]

ProteinModelPortal

Q16875.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-33964N.

IntAct

Q16875. 5 interactions.

STRING

9606.ENSP00000369100.

PTM databases

PhosphoSite

Q16875.

Polymorphism databases

DMDM

3023733.

Proteomic databases

PaxDb

Q16875.

PRIDE

Q16875.

Protocols and materials databases

DNASU

5209.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000358499; ENSP00000351288; ENSG00000170525.
ENST00000360521; ENSP00000353712; ENSG00000170525.
ENST00000379775; ENSP00000369100; ENSG00000170525.

GeneID

5209.

KEGG

hsa:5209.

UCSC

uc001ije.3. human.
uc001ijf.3. human.

Organism-specific databases

CTD

5209.

GeneCards

GC10P006186.

HGNC

HGNC:8874. PFKFB3.

HPA

CAB020795.
HPA008266.

MIM

605319. gene.

neXtProt

NX_Q16875.

PharmGKB

PA33213.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0406.

HOGENOM

HOG000181112.

HOVERGEN

HBG005628.

KO

K01103.

PhylomeDB

Q16875.

Enzyme and pathway databases

BRENDA

2.7.1.105. 2681.

Pathway_Interaction_DB

hif1_tfpathway. HIF-1-alpha transcription factor network.

Reactome

REACT_111217. Metabolism.

SABIO-RK

Q16875.

Gene expression databases

ArrayExpress

Q16875.

Bgee

Q16875.

CleanEx

HS_PFKFB3.

Genevestigator

Q16875.

GermOnline

ENSG00000170525. 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

Pfkfb3. human.

EvolutionaryTrace

Q16875.

GenomeRNAi

5209.

NextBio

20146.

SOURCE

Search...

Entry information

Entry name

F263_HUMAN

Accession

Primary (citable) accession number: Q16875
Secondary accession number(s): O43622, O75902, Q5VX19

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	November 1, 1996
Last modified:	May 1, 2013
This is version 135 of the entry and version 1 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.