Reviewed, UniProtKB/Swiss-Prot P25114 (F264_RAT)

Names and origin

Protein names

Recommended name:
    6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4
Alternative name(s):
    6PF-2-K/Fru-2,6-P2ASE testis-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:

Pfkfb4

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	469 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	The most important regulatory mechanism of these opposing activities is by phosphorylation and dephosphorylation of the enzyme.
Subunit structure	Homodimer.
Tissue specificity	Testis.
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 Multifunctional enzyme
Gene Ontology (GO)
Biological process	fructose 2,6-bisphosphate metabolic process Inferred from electronic annotation. Source: InterPro
Molecular function	6-phosphofructo-2-kinase activity Ref.1 Inferred from direct assay. Source: RGD ATP binding Inferred from electronic annotation. Source: UniProtKB-KW fructose-2,6-bisphosphate 2-phosphatase activity Ref.1 Inferred from direct assay. Source: RGD identical protein binding Ref.2 Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		1	EBI-728132,EBI-728132

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed

Chain

2 – 469

468

6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4

PRO_0000179971

Regions

Nucleotide binding

46 – 53

8

ATP Potential

Region

2 – 249

248

6-phosphofructo-2-kinase

Region

250 – 469

220

Fructose-2,6-bisphosphatase

Sites

Active site

129

1

Potential

Active site

159

1

Potential

Active site

257

1

Tele-phosphohistidine intermediate

Active site

326

1

Potential

Active site

391

1

Proton donor By similarity

Binding site

103

1

Fructose-6-phosphate By similarity

Binding site

194

1

Fructose-6-phosphate By similarity

Amino acid modifications

Modified residue

29

1

Phosphoserine; by PKC Potential

Modified residue

444

1

Phosphothreonine; by PKC Potential

Secondary structure

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469

Helix Strand Turn

Details...

Beta strand

40 – 45

6

Helix

52 – 65

14

Beta strand

70 – 74

5

Helix

75 – 83

9

Helix

89 – 92

4

Helix

97 – 119

23

Beta strand

124 – 130

7

Helix

135 – 148

14

Beta strand

151 – 157

7

Helix

162 – 172

11

Turn

173 – 175

3

Turn

177 – 181

5

Helix

184 – 199

16

Turn

207 – 212

6

Beta strand

215 – 218

4

Turn

220 – 222

3

Beta strand

223 – 228

6

Helix

233 – 242

10

Beta strand

252 – 256

5

Helix

261 – 265

5

Helix

276 – 292

17

Beta strand

298 – 301

4

Helix

305 – 311

7

Beta strand

314 – 316

3

Helix

322 – 324

3

Helix

330 – 332

3

Helix

337 – 343

7

Helix

345 – 353

9

Turn

355 – 357

3

Helix

366 – 382

17

Beta strand

384 – 390

7

Helix

392 – 402

11

Turn

407 – 409

3

Helix

410 – 412

3

Beta strand

419 – 425

7

Beta strand

427 – 436

10

Helix

458 – 461

4

Sequences

	Sequence		Length	Mass (Da)
	P25114-1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: E3D0AF34D3A09CA6	FASTA	469	54,155
	10 20 30 40 50 60 MASPRELTQN PLKKIWMPYS NGRPALHASQ RGVCMTNCPT LIVMVGLPAR GKTYISKKLT 70 80 90 100 110 120 RYLNWIGVPT REFNVGQYRR DMVKTYKSFE FFLPDNEEGL KIRKQCALAA LNDVRKFLSE 130 140 150 160 170 180 EGGHVAVFDA TNTTRERRAM IFNFGEQNGY KTFFVESICV DPEVIAANIV QVKLGSPDYV 190 200 210 220 230 240 NRDSDEATED FMRRIECYEN SYESLDEEQD RDLSYIKIMD VGQSYVVNRV ADHIQSRIVY 250 260 270 280 290 300 YLMNIHVTPR SIYLCRHGES ELNLKGRIGG DPGLSPRGRE FSKHLAQFIS DQNIKDLKVW 310 320 330 340 350 360 TSQMKRTIQT AEALSVPYEQ WKVLNEIDAG VCEEMTYEEI QDHYPLEFAL RDQDKYRYRY 370 380 390 400 410 420 PKGESYEDLV QRLEPVIMEL ERQENVLVIC HQAVMRCLLA YFLDKAAEEL PYLKCPLHTV 430 440 450 460 LKLTPVAYGC KVESIFLNVA AVNTHRDRPQ NVDISRPSEE ALVTVPAHQ

References

[1]	"Molecular cloning of the DNA and expression and characterization of rat testes fructose-6-phosphate,2-kinase:fructose-2,6-bisphosphatase." Sakata J., Abe Y., Uyeda K. J. Biol. Chem. 266:15764-15770(1991) [PubMed: 1651918] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Testis.
[2]	"The crystal structure of the bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase reveals distinct domain homologies." Hasemann C.A., Istvan E.S., Uyeda K., Deisenhofer J. Structure 4:1017-1029(1996) [PubMed: 8805587] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS). Tissue: Testis.
[3]	"Crystal structure of the H256A mutant of rat testis fructose-6-phosphate,2-kinase/fructose-2,6-bisphosphatase. Fructose 6-phosphate in the active site leads to mechanisms for both mutant and wild type bisphosphatase activities." Yuen M.H., Mizuguchi H., Lee Y.H., Cook P.F., Uyeda K., Hasemann C.A. J. Biol. Chem. 274:2176-2184(1999) [PubMed: 9890980] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF MUTANT ALA-257. Tissue: Testis.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

M64797 mRNA. Translation: AAA41163.1.

IPI

IPI00230820.

PIR

A40800.

RefSeq

NP_062206.1.

UniGene

Rn.90092

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BIF	X-ray	2.00	A	1-469	[»]
2BIF	X-ray	2.40	A/B	1-469	[»]
3BIF	X-ray	2.30	A	2-468	[»]

ModBase

Search...

Genome annotation databases

Ensembl

ENSRNOG00000020656. Rattus norvegicus. [Contig view]

GeneID

54283.

KEGG

rno:54283.

Organism-specific databases

RGD

3310. Pfkfb4.

Phylogenomic databases

HOVERGEN

P25114.

OMA

P25114. SYETLDE.

Enzyme and pathway databases

BRENDA

2.7.1.105. 248.
3.1.3.46. 248.

Gene expression databases

ArrayExpress

P25114.

GermOnline

ENSRNOG00000020656. Rattus norvegicus.

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

610862.

Entry information

Entry name

F264_RAT

Accession

Primary (citable) accession number: P25114

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 1992
Last sequence update:	January 23, 2007
Last modified:	June 16, 2009
This is version 87 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)