Q16877 (F264_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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. 6-phosphofructo-2-kinase
   EC=2.7.1.105
2. Fructose-2,6-bisphosphatase
   EC=3.1.3.46

Gene names

Name:

PFKFB4

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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.
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	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Hydrolase Kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Biological process	fructose 2,6-bisphosphate metabolic process Non-traceable author statement. Source: UniProtKB glycolysis 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.2. 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...

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_0000179970
Regions
	Nucleotide binding	46 – 53	8	ATP By similarity
	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	444	1	Phosphothreonine; by PKC Potential
Natural variations
	Natural variant	181	1	N → K in a breast cancer sample; somatic mutation. Ref.7		VAR_036075

Sequences

	Sequence		Length	Mass (Da)
	Q16877 [UniParc]. Last modified January 23, 2007. Version 6. Checksum: 7E190C3C0A197D9F	FASTA	469	54,040
	10 20 30 40 50 60 MASPRELTQN PLKKIWMPYS NGRPALHACQ RGVCMTNCPT LIVMVGLPAR GKTYISKKLT 70 80 90 100 110 120 RYLNWIGVPT REFNVGQYRR DVVKTYKSFE FFLPDNEEGL KIRKQCALAA LRDVRRFLSE 130 140 150 160 170 180 EGGHVAVFDA TNTTRERRAT IFNFGEQNGY KTFFVESICV DPEVIAANIV QVKLGSPDYV 190 200 210 220 230 240 NRDSDEATED FMRRIECYEN SYESLDEDLD RDLSYIKIMD VGQSYVVNRV ADHIQSRIVY 250 260 270 280 290 300 YLMNIHVTPR SIYLCRHGES ELNLKGRIGG DPGLSPRGRE FAKSLAQFIS DQNIKDLKVW 310 320 330 340 350 360 TSQMKRTIQT AEALGVPYEQ WKVLNEIDAG VCEEMTYEEI QDNYPLEFAL RDQDKYRYRY 370 380 390 400 410 420 PKGESYEDLV QRLEPVIMEL ERQENVLVIC HQAVMRCLLA YFLDKAAEQL PYLKCPLHTV 430 440 450 460 LKLTPVAYGC KVESIFLNVA AVNTHRDRPQ NVDISRPPEE ALVTVPAHQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	Sakakibara R. Submitted (MAR-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Cloning, expression and chromosomal localization of a human testis 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene." Manzano A., Perez J.X., Nadal M., Estivill X., Lange A., Bartrons R. Gene 229:83-89(1999) [PubMed: 10095107] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Testis.
[3]	"Specific expression of pfkfb4 gene in spermatogonia germ cells and analysis of its 5'-flanking region." Gomez M., Manzano A., Navarro-Sabate A., Duran J., Obach M., Perales J.C., Bartrons R. FEBS Lett. 579:357-362(2005) [PubMed: 15642344] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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]. Tissue: Placenta.
[6]	"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: 8830046] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 357-469. Tissue: Placenta.
[7]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] LYS-181.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D49818 mRNA. Translation: BAA18921.1. AF108765 mRNA. Translation: AAD09427.1. AY786551 Genomic DNA. Translation: AAV65753.1. CH471055 Genomic DNA. Translation: EAW64890.1. BC010269 mRNA. Translation: AAH10269.1.
IPI	IPI00220070.
PIR	JC5871.
RefSeq	NP_004558.1. NM_004567.2.
UniGene	Hs.476217.
3D structure databases
ProteinModelPortal	Q16877.
SMR	Q16877. Positions 6-469.
ModBase	Search...
Protein-protein interaction databases
STRING	Q16877.
PTM databases
PhosphoSite	Q16877.
Polymorphism databases
DMDM	6226609.
Proteomic databases
PRIDE	Q16877.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000232375; ENSP00000232375; ENSG00000114268.
GeneID	5210.
KEGG	hsa:5210.
UCSC	uc003ctv.1. human.
Organism-specific databases
CTD	5210.
GeneCards	GC03M048530.
H-InvDB	HIX0200535.
HGNC	HGNC:8875. PFKFB4.
MIM	605320. gene.
neXtProt	NX_Q16877.
PharmGKB	PA33214.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG17760.
HOGENOM	HBG395770.
HOVERGEN	HBG005628.
InParanoid	Q16877.
OMA	YETLDEN.
OrthoDB	EOG4HX50X.
PhylomeDB	Q16877.
Enzyme and pathway databases
BRENDA	3.1.3.46. 2681.
Reactome	REACT_474. Metabolism of carbohydrates.
Gene expression databases
ArrayExpress	Q16877.
Bgee	Q16877.
CleanEx	HS_PFKFB4.
Genevestigator	Q16877.
GermOnline	ENSG00000114268. 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]
KO	K01103.
PANTHER	PTHR10606. 6Pfruct_kin. 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
NextBio	20150.
SOURCE	Search...

Entry information

Entry name

F264_HUMAN

Accession

Primary (citable) accession number: Q16877
Secondary accession number(s): Q5S3G5

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	January 23, 2007
Last modified:	December 14, 2011
This is version 113 of the entry and version 6 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.