Reviewed, UniProtKB/Swiss-Prot P16118 (F261_HUMAN)

Names and origin

Protein names

Recommended name:
    6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 1
Alternative name(s):
    6PF-2-K/Fru-2,6-P2ASE liver 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:	PFKFB1
Synonyms:	F6PK, PFRX

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	471 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 inhibition of the kinase activity.
Subunit structure	Homodimer.
Tissue specificity	Liver.
Sequence similarities	In the C-terminal section; belongs to the phosphoglycerate mutase family.

Ontologies

Keywords
Ligand	ATP-binding Nucleotide-binding
Molecular function	Hydrolase Kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Multifunctional enzyme
Gene Ontology (GO)
Biological process	fructose 2,6-bisphosphate metabolic process Ref.5 Inferred from direct assay. Source: UniProtKB gluconeogenesis Traceable author statement. Source: UniProtKB glycolysis Traceable author statement. Source: UniProtKB protein kinase cascade Inferred from Experiment. Source: Reactome
Cellular component	6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 1 complex Inferred from direct assay. Source: UniProtKB
Molecular function	6-phosphofructo-2-kinase activity Ref.5 Traceable author statement. Source: UniProtKB ATP binding Inferred from electronic annotation. Source: UniProtKB-KW fructose-2,6-bisphosphate 2-phosphatase activity Ref.5 Inferred from direct assay. Source: UniProtKB identical protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		1	EBI-709807,EBI-709807
GCK	P35557	2	EBI-709807,EBI-709928

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 471

471

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

PRO_0000179960

Regions

Nucleotide binding

49 – 56

8

ATP Potential

Region

1 – 250

250

6-phosphofructo-2-kinase

Region

251 – 471

221

Fructose-2,6-bisphosphatase

Sites

Active site

131

1

Potential

Active site

161

1

Potential

Active site

259

1

Tele-phosphohistidine intermediate By similarity

Active site

328

1

Potential

Active site

393

1

Proton donor By similarity

Binding site

105

1

Fructose-6-phosphate By similarity

Binding site

196

1

Fructose-6-phosphate By similarity

Amino acid modifications

Modified residue

33

1

Phosphoserine; by PKA By similarity

Experimental info

Sequence conflict

305

1

H → R in CAA36861. Ref.1

Sequence conflict

359

1

R → H in AAA35818. Ref.5

Sequence conflict

397 – 398

2

MR → HA in AAA35818. Ref.5

Secondary structure

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471

Helix Strand Turn

Details...

Beta strand

43 – 48

6

Helix

55 – 68

14

Beta strand

73 – 77

5

Helix

78 – 83

6

Helix

91 – 94

4

Helix

99 – 121

23

Beta strand

126 – 132

7

Helix

137 – 150

14

Beta strand

153 – 160

8

Helix

164 – 175

12

Helix

187 – 201

15

Turn

209 – 214

6

Beta strand

217 – 221

5

Turn

222 – 225

4

Beta strand

226 – 230

5

Helix

235 – 244

10

Beta strand

254 – 258

5

Helix

263 – 266

4

Helix

278 – 293

16

Beta strand

300 – 303

4

Helix

307 – 314

8

Helix

324 – 326

3

Helix

332 – 334

3

Helix

339 – 345

7

Helix

347 – 355

9

Turn

357 – 359

3

Helix

368 – 384

17

Beta strand

386 – 392

7

Helix

394 – 405

12

Turn

409 – 411

3

Helix

412 – 414

3

Beta strand

421 – 427

7

Beta strand

429 – 438

10

Helix

460 – 464

5

Sequences

	Sequence		Length	Mass (Da)
	P16118-1 [UniParc]. Last modified November 1, 1997. Version 3. Checksum: C4FF081A295FB7D3	FASTA	471	54,681
	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

References

	« Hide 'large scale' referencesShow '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: 2163524] [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. , 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: 14702039] [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. , 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: 15772651] [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: 15489334] [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: 2837207] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 94-471. Tissue: Liver.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.

IPI

IPI00783603.

PIR

S12732.

RefSeq

NP_002616.2.

UniGene

Hs.444304

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1K6M	X-ray	2.40	A/B	40-471	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P16118. 3 interactions.

PTM databases

PhosphoSite

P16118.

Proteomic databases

PRIDE

P16118.

Genome annotation databases

Ensembl

ENSG00000158571. Homo sapiens. [Contig view]

GeneID

5207.

KEGG

hsa:5207.

UCSC

uc004dty.1. human.

Organism-specific databases

GeneCards

GC0XM054976.

H-InvDB

HIX0056283.

HGNC

HGNC:8872. PFKFB1.

HPA

HPA013959.

MIM

311790. gene.

PharmGKB

PA33211.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P16118.

HOVERGEN

P16118.

OMA

P16118. TTHARRQ.

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

P16118.

Bgee

P16118.

CleanEx

HS_PFKFB1.

GermOnline

ENSG00000158571. 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

20136.

SOURCE

Search...

Entry information

Entry name

F261_HUMAN

Accession

Primary (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:	July 7, 2009
This is version 106 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)