Reviewed, UniProtKB/Swiss-Prot Q6DTY7 (F264_MOUSE)

Names and origin

Protein names

Recommended name:
    6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4
      Short name=6PF-2-K/Fru-2,6-P2ase 4
      Short name=PFK/FBPase 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

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

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

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 transcript level.

General annotation (Comments)

Function	Synthesis and degradation of fructose 2,6-bisphosphate By similarity.
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 By similarity.
Subunit structure	Homodimer By similarity.
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	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 Inferred from electronic annotation. Source: EC 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 6 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q6DTY7-1)

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: Q6DTY7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-218: Missing.

Isoform 3 (identifier: Q6DTY7-3)

The sequence of this isoform differs from the canonical sequence as follows:
     358-469: YRYPKGESYE...EALVTVPAHQ → PMKTWCSGWS...PTSNAPCTQS

Isoform 4 (identifier: Q6DTY7-4)

The sequence of this isoform differs from the canonical sequence as follows:
     212-221: DLSYIKIMDV → SSGQSRRLFS
     222-469: Missing.

Isoform 5 (identifier: Q6DTY7-5)

The sequence of this isoform differs from the canonical sequence as follows:
     33-48: Missing.

Isoform 6 (identifier: Q6DTY7-6)

The sequence of this isoform differs from the canonical sequence as follows:
     1-34: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 469	468	6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4		PRO_0000268187
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 By similarity
	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
Natural variations
	Alternative sequence	1 – 218	218	Missing in isoform 2.		VSP_021959
	Alternative sequence	1 – 34	34	Missing in isoform 6.		VSP_021960
	Alternative sequence	33 – 48	16	Missing in isoform 5.		VSP_021961
	Alternative sequence	212 – 221	10	DLSYIKIMDV → SSGQSRRLFS in isoform 4.		VSP_021962
	Alternative sequence	222 – 469	248	Missing in isoform 4.		VSP_021963
	Alternative sequence	358 – 469	112	YRYPK…VPAHQ → PMKTWCSGWSPSSWNWRGRR MCWSFATRLSCAASWPTSLT RQLKSCPTSNAPCTQS in isoform 3.		VSP_021964

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 23, 2007. Version 4. Checksum: 53777000F163DDE7	FASTA	469	54,067
	10 20 30 40 50 60 MASPRELTQN PLKKIWMPYS NGRPALHASQ RGVCMTNCPT LIVMVGLPAR GKTYISKKLT 70 80 90 100 110 120 RYLNWIGVPT REFNVGQYRR DIVKTYKSFE FFLPDNEEGL KIRKQCALAA LSDVRKFLSE 130 140 150 160 170 180 EGGHVAVFDA TNTTRERRAM IFNFGEQNGY KTFFVESICV DPEVVAANIV QVKLGSPDYV 190 200 210 220 230 240 NRDSDEATED FMRRIECYEN SYESLDEDLD 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
	Isoform 2. Checksum: 2DE38D2AF5D41D05	FASTA	251	29,036
	10 20 30 40 50 60 MDVGQSYVVN RVADHIQSRI VYYLMNIHVT PRSIYLCRHG ESELNLKGRI GGDPGLSPRG 70 80 90 100 110 120 REFSKHLAQF ISDQNIKDLK VWTSQMKRTI QTAEALSVPY EQWKVLNEID AGVCEEMTYE 130 140 150 160 170 180 EIQDHYPLEF ALRDQDKYRY RYPKGESYED LVQRLEPVIM ELERQENVLV ICHQAVMRCL 190 200 210 220 230 240 LAYFLDKAAE ELPYLKCPLH TVLKLTPVAY GCKVESIFLN VAAVNTHRDR PQNVDISRPS 250 EEALVTVPAH Q
	Isoform 3. Checksum: 168599E96293CB8E	FASTA	413	47,601
	10 20 30 40 50 60 MASPRELTQN PLKKIWMPYS NGRPALHASQ RGVCMTNCPT LIVMVGLPAR GKTYISKKLT 70 80 90 100 110 120 RYLNWIGVPT REFNVGQYRR DIVKTYKSFE FFLPDNEEGL KIRKQCALAA LSDVRKFLSE 130 140 150 160 170 180 EGGHVAVFDA TNTTRERRAM IFNFGEQNGY KTFFVESICV DPEVVAANIV QVKLGSPDYV 190 200 210 220 230 240 NRDSDEATED FMRRIECYEN SYESLDEDLD 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 RDQDKYRPMK 370 380 390 400 410 TWCSGWSPSS WNWRGRRMCW SFATRLSCAA SWPTSLTRQL KSCPTSNAPC TQS
	Isoform 4. Checksum: 021463A4216FB0DC	FASTA	221	25,322
	10 20 30 40 50 60 MASPRELTQN PLKKIWMPYS NGRPALHASQ RGVCMTNCPT LIVMVGLPAR GKTYISKKLT 70 80 90 100 110 120 RYLNWIGVPT REFNVGQYRR DIVKTYKSFE FFLPDNEEGL KIRKQCALAA LSDVRKFLSE 130 140 150 160 170 180 EGGHVAVFDA TNTTRERRAM IFNFGEQNGY KTFFVESICV DPEVVAANIV QVKLGSPDYV 190 200 210 220 NRDSDEATED FMRRIECYEN SYESLDEDLD RSSGQSRRLF S
	Isoform 5. Checksum: 45892FD5B58EB548	FASTA	453	52,394
	10 20 30 40 50 60 MASPRELTQN PLKKIWMPYS NGRPALHASQ RGARGKTYIS KKLTRYLNWI GVPTREFNVG 70 80 90 100 110 120 QYRRDIVKTY KSFEFFLPDN EEGLKIRKQC ALAALSDVRK FLSEEGGHVA VFDATNTTRE 130 140 150 160 170 180 RRAMIFNFGE QNGYKTFFVE SICVDPEVVA ANIVQVKLGS PDYVNRDSDE ATEDFMRRIE 190 200 210 220 230 240 CYENSYESLD EDLDRDLSYI KIMDVGQSYV VNRVADHIQS RIVYYLMNIH VTPRSIYLCR 250 260 270 280 290 300 HGESELNLKG RIGGDPGLSP RGREFSKHLA QFISDQNIKD LKVWTSQMKR TIQTAEALSV 310 320 330 340 350 360 PYEQWKVLNE IDAGVCEEMT YEEIQDHYPL EFALRDQDKY RYRYPKGESY EDLVQRLEPV 370 380 390 400 410 420 IMELERQENV LVICHQAVMR CLLAYFLDKA AEELPYLKCP LHTVLKLTPV AYGCKVESIF 430 440 450 LNVAAVNTHR DRPQNVDISR PSEEALVTVP AHQ
	Isoform 6. Checksum: A87B2F6B22059987	FASTA	435	50,246
	10 20 30 40 50 60 MTNCPTLIVM VGLPARGKTY ISKKLTRYLN WIGVPTREFN VGQYRRDIVK TYKSFEFFLP 70 80 90 100 110 120 DNEEGLKIRK QCALAALSDV RKFLSEEGGH VAVFDATNTT RERRAMIFNF GEQNGYKTFF 130 140 150 160 170 180 VESICVDPEV VAANIVQVKL GSPDYVNRDS DEATEDFMRR IECYENSYES LDEDLDRDLS 190 200 210 220 230 240 YIKIMDVGQS YVVNRVADHI QSRIVYYLMN IHVTPRSIYL CRHGESELNL KGRIGGDPGL 250 260 270 280 290 300 SPRGREFSKH LAQFISDQNI KDLKVWTSQM KRTIQTAEAL SVPYEQWKVL NEIDAGVCEE 310 320 330 340 350 360 MTYEEIQDHY PLEFALRDQD KYRYRYPKGE SYEDLVQRLE PVIMELERQE NVLVICHQAV 370 380 390 400 410 420 MRCLLAYFLD KAAEELPYLK CPLHTVLKLT PVAYGCKVES IFLNVAAVNT HRDRPQNVDI 430 SRPSEEALVT VPAHQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Hypoxic regulation of the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene family (PFKFB-1-4) expression in vivo." Minchenko O.H., Opentanova I.L., Caro J. FEBS Lett. 554:264-270(2003) [PubMed: 14623077] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Strain: C57BL/6. Tissue: Testis.
[2]	"Splice isoform of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-4: expression and hypoxic regulation." Minchenko O.H., Ogura T., Opentanova I.L., Minchenko D.O., Esumi H. Mol. Cell. Biochem. 280:227-234(2005) [PubMed: 16311927] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6). Strain: C57BL/6. Tissue: Testis.
[3]	"Alternative splice isoforms of mouse 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4." Minchenko D.O., Opentanova I.L., Minchenko O.H. Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3 AND 4). Strain: C57BL/6. Tissue: Testis.
[4]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Strain: NOD.
[5]	"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] (ISOFORM 5). Strain: C57BL/6. Tissue: Brain.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY646092 mRNA. Translation: AAT72897.2. AY707862 mRNA. Translation: AAU88258.1. DQ350638 mRNA. Translation: ABC71307.1. AY756065 mRNA. Translation: AAV32501.1. AY756066 mRNA. Translation: AAV32502.1. AY756067 mRNA. Translation: AAV32503.1. AK155172 mRNA. Translation: BAE33093.1. BC057594 mRNA. Translation: AAH57594.1.
IPI	IPI00465760. IPI00720247. IPI00816846. IPI00816868. IPI00816913. IPI00817003.
RefSeq	NP_766607.3.
UniGene	Mm.132391
3D structure databases
HSSP	HSSP built from PDB template 1BIF based on UniProtKB P25114.
SMR	Q6DTY7. Positions 6-448, 38-469.
ModBase	Search...
Protein-protein interaction databases
STRING	Q6DTY7.
PTM databases
PhosphoSite	Q6DTY7.
Proteomic databases
PRIDE	Q6DTY7.
Genome annotation databases
Ensembl	ENSMUST00000051873; ENSMUSP00000057197; ENSMUSG00000025648; Mus musculus. [Genome view] ENSMUST00000098369; ENSMUSP00000095971; ENSMUSG00000025648; Mus musculus. [Genome view]
GeneID	270198.
KEGG	mmu:270198.
UCSC	uc009rri.1. mouse. uc009rrk.1. mouse. uc009rrl.1. mouse.
Organism-specific databases
CTD	270198.
MGI	MGI:2687284. Pfkfb4.
Phylogenomic databases
eggNOG	roNOG14054.
HOGENOM	HBG395770.
HOVERGEN	Q6DTY7.
InParanoid	Q6DTY7.
OMA	SYETLDE.
OrthoDB	EOG9F4VWQ.
PhylomeDB	Q6DTY7.
Enzyme and pathway databases
BRENDA	2.7.1.105. 244. 3.1.3.46. 244.
Gene expression databases
ArrayExpress	Q6DTY7.
Bgee	Q6DTY7.
Genevestigator	Q6DTY7.
GermOnline	ENSMUSG00000025648. Mus musculus.
Family and domain databases
InterPro	IPR003094. 6Pfruct_kin. IPR013079. 6Phosfructo_kin. IPR016260. Bifunct_6PFK/fruc_bisP_Ptase. IPR001345. PG/BPGM_mutase_AS. 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.
SMART	SM00855. PGAM. 1 hit. [Graphical view]
PROSITE	PS00175. PG_MUTASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	393301.
SOURCE	Search...

Entry information

Entry name

F264_MOUSE

Accession

Primary (citable) accession number: Q6DTY7
Secondary accession number(s): Q5UD55 , Q5UD56, Q5UD57, Q5Y296, Q6PFE8

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 12, 2006
Last sequence update:	January 23, 2007
Last modified:	February 9, 2010
This is version 49 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)