P07953 (F261_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	471 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
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
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Nucleotide-binding
Molecular function	Hydrolase Kinase Transferase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Biological_process	fructose 2,6-bisphosphate metabolic process Inferred from sequence or structural similarity. Source: UniProtKB fructose metabolic process Inferred from electronic annotation. Source: InterPro organ regeneration Inferred from expression pattern PubMed 1315037. Source: RGD positive regulation of glucokinase activity Inferred from mutant phenotype PubMed 15047617. Source: RGD response to cAMP Inferred from expression pattern PubMed 7593243. Source: RGD response to glucagon stimulus Inferred from expression pattern PubMed 7593243. Source: RGD response to glucocorticoid stimulus Inferred from expression pattern PubMed 7593243PubMed 8131849. Source: RGD response to insulin stimulus Inferred from expression pattern PubMed 8131849. Source: RGD response to starvation Inferred from expression pattern PubMed 9705027. Source: RGD
Cellular_component	6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 1 complex Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	6-phosphofructo-2-kinase activity Inferred from direct assay PubMed 7619077. Source: RGD ATP binding Inferred from direct assay PubMed 7619077. Source: RGD fructose-2,6-bisphosphate 2-phosphatase activity Inferred from sequence or structural similarity. Source: UniProtKB fructose-6-phosphate binding Inferred from direct assay PubMed 7619077. Source: RGD identical protein binding Inferred from direct assay PubMed 7619077. Source: RGD
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		2	EBI-709873,EBI-709873

Alternative products

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

Isoform 1 (identifier: P07953-1)

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: P07953-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-33: MSREMGELTQTRLQKIWIPHSSSSSVLQRRRGS → MEEKASKRTA

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.8

Chain

2 – 471

470

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

PRO_0000179962

Regions

Nucleotide binding

49 – 56

8

ATP By similarity

Region

2 – 250

249

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

Active site

328

1

Potential

Active site

393

1

Proton donor

Binding site

105

1

Fructose-6-phosphate By similarity

Binding site

196

1

Fructose-6-phosphate By similarity

Amino acid modifications

Modified residue

2

1

N-acetylserine Ref.5

Modified residue

33

1

Phosphoserine; by PKA

Natural variations

Alternative sequence

1 – 33

33

MSREM…RRRGS → MEEKASKRTA in isoform 2.

VSP_004674

Experimental info

Sequence conflict

135

1

T → Y Ref.3

Sequence conflict

135

1

T → Y Ref.4

Sequence conflict

135

1

T → Y Ref.5

Sequence conflict

138

1

E → F Ref.3

Sequence conflict

257

1

Missing AA sequence Ref.7

Secondary structure

1

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471

Helix Strand Turn

Details...

Beta strand

253 – 258

6

Helix

263 – 267

5

Helix

278 – 292

15

Beta strand

300 – 306

7

Helix

307 – 314

8

Turn

315 – 317

3

Beta strand

321 – 323

3

Helix

324 – 326

3

Helix

332 – 334

3

Helix

339 – 345

7

Helix

347 – 355

9

Turn

357 – 359

3

Helix

368 – 374

7

Helix

376 – 383

8

Beta strand

386 – 392

7

Helix

394 – 404

11

Turn

409 – 411

3

Helix

412 – 414

3

Beta strand

421 – 428

8

Beta strand

431 – 438

8

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: E307AF13945E0FCD	FASTA	471	54,763
	10 20 30 40 50 60 MSREMGELTQ TRLQKIWIPH SSSSSVLQRR RGSSIPQFTN SPTMVIMVGL PARGKTYIST 70 80 90 100 110 120 KLTRYLNWIG TPTKVFNLGQ YRREAVSYRN YEFFRPDNTE AQLIRKQCAL AALKDVHKYL 130 140 150 160 170 180 SREEGHVAVF DATNTTRERR SLILQFAKEH GYKVFFIESI CNDPEIIAEN IKQVKLGSPD 190 200 210 220 230 240 YIDCDQEKVL EDFLKRIECY EINYQPLDEE LDSHLSYIKI FDVGTRYMVN RVQDHVQSRT 250 260 270 280 290 300 AYYLMNIHVT PRSIYLCRHG ESELNLRGRI GGDSGLSARG KQYAYALANF IRSQGISSLK 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 GCRVESIYLN VEAVNTHRDK PENVDITREA EEALDTVPAH Y
	Isoform 2 [UniParc]. Checksum: 3DCD00D54929917D	FASTA	448	52,070
	10 20 30 40 50 60 MEEKASKRTA SIPQFTNSPT MVIMVGLPAR GKTYISTKLT RYLNWIGTPT KVFNLGQYRR 70 80 90 100 110 120 EAVSYRNYEF FRPDNTEAQL IRKQCALAAL KDVHKYLSRE EGHVAVFDAT NTTRERRSLI 130 140 150 160 170 180 LQFAKEHGYK VFFIESICND PEIIAENIKQ VKLGSPDYID CDQEKVLEDF LKRIECYEIN 190 200 210 220 230 240 YQPLDEELDS HLSYIKIFDV GTRYMVNRVQ DHVQSRTAYY LMNIHVTPRS IYLCRHGESE 250 260 270 280 290 300 LNLRGRIGGD SGLSARGKQY AYALANFIRS QGISSLKVWT SHMKRTIQTA EALGVPYEQW 310 320 330 340 350 360 KALNEIDAGV CEEMTYEEIQ EHYPEEFALR DQDKYRYRYP KGESYEDLVQ RLEPVIMELE 370 380 390 400 410 420 RQENVLVICH QAVMRCLLAY FLDKSSDELP YLKCPLHTVL KLTPVAYGCR VESIYLNVEA 430 440 VNTHRDKPEN VDITREAEEA LDTVPAHY

References

[1]	"Complete nucleotide sequence coding for rat liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase derived from a cDNA clone." Darville M.I., Crepin K.M., Vandekerckhove J., van Damme J., Octave J.-N., Rider M.H., Marchand M.J., Hue L., Rousseau G.G. FEBS Lett. 224:317-321(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 1), PROTEIN SEQUENCE OF 16-29; 65-74; 90-105; 123-137; 189-195; 240-252; 259-266 AND 309-324 (ISOFORM 1). Strain: Wistar. Tissue: Liver.
[2]	"Isolation of a cDNA clone for rat liver 6-phosphofructo 2-kinase/fructose 2,6-bisphosphatase." Colosa A.D., Lively M.O., El-Maghrabi M.R., Pilkis S.J. Biochem. Biophys. Res. Commun. 143:1092-1098(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 1). Strain: Sprague-Dawley.
[3]	"Characterization of distinct mRNAs coding for putative isozymes of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase." Crepin K.M., Darville M.I., Hue L., Rousseau G.G. Eur. J. Biochem. 183:433-440(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). Strain: Wistar. Tissue: Liver.
[4]	"Induction of rat liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase mRNA by refeeding and insulin." Colosia A.D., Marker A.J., Lange A.J., El-Maghrabi M.R., Granner D.K., Tauler A., Pilkis J., Pilkis S.J. J. Biol. Chem. 263:18669-18677(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Liver.
[5]	"Complete amino acid sequence of rat liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase." Lively M.O., El-Maghrabi M.R., Pilkis J., D'Angelo G., Colosia A.D., Ciavola J.A., Fraser B.A., Pilkis S.J. J. Biol. Chem. 263:839-849(1988) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE (ISOFORM 1), ACETYLATION AT SER-2. Tissue: Liver.
[6]	"Cloning and expression in Escherichia coli of a rat hepatoma cell cDNA coding for 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase." Crepin K.M., Darville M.I., Michel A., Hue L., Rousseau G.G. Biochem. J. 264:151-160(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 2). Strain: Wistar. Tissue: Liver.
[7]	"Active site sequence of hepatic fructose-2,6-bisphosphatase. Homology in primary structure with phosphoglycerate mutase." Pilkis S.J., Lively M.O., El-Maghrabi M.R. J. Biol. Chem. 262:12672-12675(1987) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 220-267. Tissue: Liver.
[8]	"5' flanking sequence and structure of a gene encoding rat 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase." Darville M.I., Crepin K.M., Hue L., Rousseau G.G. Proc. Natl. Acad. Sci. U.S.A. 86:6543-6547(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-32 (ISOFORM 1), PROTEIN SEQUENCE OF 2-10 (ISOFORM 2).
[9]	"Evolution of a bifunctional enzyme: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase." Bazan J.F., Fletterick R.J., Pilkis S.J. Proc. Natl. Acad. Sci. U.S.A. 86:9642-9646(1989) [PubMed] [Europe PMC] [Abstract] Cited for: DOMAINS.
[10]	"Catalytic site of rat liver and bovine heart fructose-6-phosphate,2-kinase:fructose-2,6-bisphosphatase. Identification of fructose 6-phosphate binding site." Kitamura K., Uyeda K., Hartman F.C., Kangawa K., Matsuo H. J. Biol. Chem. 264:6344-6348(1989) [PubMed] [Europe PMC] [Abstract] Cited for: FRUCTOSE-6-P BINDING SITES.
[11]	"Crystal structure of the rat liver fructose-2,6-bisphosphatase based on selenomethionine multiwavelength anomalous dispersion phases." Lee Y.-H., Ogata C., Pflugrath J.W., Levitt D.G., Sarma R., Banaszak L.J., Pilkis S.J. Biochemistry 35:6010-6019(1996) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS). Tissue: Liver.
[12]	"Crystal structure of a trapped phosphoenzyme during a catalytic reaction." Lee Y.-H., Olson T.W., Ogata C.M., Levitt D.G., Banaszak L.J., Lange A.J. Nat. Struct. Biol. 4:615-618(1997) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 251-441.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Y00702 mRNA. Translation: CAA68694.1.
X15579 mRNA. Translation: CAA33606.1.
X15580 mRNA. Translation: CAA33607.1.
M26215 Genomic DNA. Translation: AAA02888.2.
M26216 Genomic DNA. Translation: AAA02889.1.
J04197 mRNA. Translation: AAA79008.1.
M27886 Genomic DNA. Translation: AAA58780.1.

IPI

IPI00327110.
IPI00393624.

PIR

KIRTFB. S11761.

RefSeq

NP_036753.4. NM_012621.4.

UniGene

Rn.10115.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1C7Z	X-ray	2.60	A/B	252-440	[»]
1C80	X-ray	2.20	A/B	252-440	[»]
1C81	X-ray	2.50	A	252-440	[»]
1FBT	X-ray	2.00	A/B	252-441	[»]
1TIP	X-ray	2.20	A/B	252-441	[»]

ProteinModelPortal

P07953.

SMR

P07953. Positions 7-471.

ModBase

Search...

Protein-protein interaction databases

IntAct

P07953. 1 interaction.

PTM databases

PhosphoSite

P07953.

Proteomic databases

PRIDE

P07953.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSRNOT00000000178; ENSRNOP00000000178; ENSRNOG00000000165.
ENSRNOT00000033656; ENSRNOP00000035212; ENSRNOG00000000165.

GeneID

24638.

KEGG

rno:24638.

Organism-specific databases

CTD

5207.

RGD

3307. Pfkfb1.

Phylogenomic databases

eggNOG

COG0406.

GeneTree

ENSGT00390000018751.

HOGENOM

HOG000181112.

HOVERGEN

HBG005628.

InParanoid

P07953.

KO

K01103.

OMA

ESELNIR.

Enzyme and pathway databases

BRENDA

3.1.3.46. 5301.

Reactome

REACT_113568. Metabolism.

SABIO-RK

P07953.

Gene expression databases

ArrayExpress

P07953.

Genevestigator

P07953.

GermOnline

ENSRNOG00000000165. Rattus norvegicus.

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

EvolutionaryTrace

P07953.

NextBio

603924.

Entry information

Entry name

F261_RAT

Accession

Primary (citable) accession number: P07953
Secondary accession number(s): P16119

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	January 23, 2007
Last modified:	April 3, 2013
This is version 144 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program