Literature summary extracted from

Chesney, J.; Clark, J.; Klarer, A.C.; Imbert-Fernandez, Y.; Lane, A.N.; Telang, S.
Fructose-2,6-bisphosphate synthesis by 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 (PFKFB4) is required for the glycolytic response to hypoxia and tumor growth (2014), Oncotarget, 5, 6670-6686.

Application

EC Number	Application	Comment	Organism
2.7.1.105	drug development	isozyme PFKFB4 appears to be a rational target for anti-neoplastic drug development	Homo sapiens
2.7.1.105	medicine	pharmacological disruption of the PFKFB4 kinase domain may have clinical utility for the treatment of human cancers	Homo sapiens
3.1.3.46	medicine	pharmacological disruption of the PFKFB4 kinase domain may have clinical utility for the treatment of human cancers	Homo sapiens

Protein Variants

EC Number	Protein Variants	Comment	Organism
2.7.1.105	additional information	stable shRNA knockdown of PFKFB4, silencing by siRNA and genomic deletion of PFKFB4 decrease fructose 2,6-bisphosphate. PFKFB4 overexpression increases fructose 2,6-bisphosphate and selective PFKFB4 inhibition in vivo markedly reduces fructose 2,6-bisphosphate, glucose uptake, and ATP levels	Homo sapiens

Metals/Ions

EC Number	Metals/Ions	Comment	Organism	Structure
2.7.1.105	Mg2+	required	Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number	Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
2.7.1.105	ATP + beta-D-fructose 6-phosphate	Homo sapiens	-	ADP + beta-D-fructose 2,6-bisphosphate	-	?
3.1.3.46	beta-D-fructose 2,6-bisphosphate + H2O	Homo sapiens	-	D-fructose 6-phosphate + phosphate	-	?

Organism

EC Number	Organism	UniProt	Comment	Textmining
2.7.1.105	Homo sapiens	Q16877	gene/isozyme Pfkfb4	-
3.1.3.46	Homo sapiens	Q16877	-	-

Source Tissue

EC Number	Source Tissue	Comment	Organism	Textmining
2.7.1.105	A-549 cell	-	Homo sapiens	-
2.7.1.105	A-549 cell	PFKFB4 is overexpressed in human cancers	Homo sapiens	-
2.7.1.105	colon	-	Homo sapiens	-
2.7.1.105	DU-145 cell	PFKFB4 is overexpressed in human cancers	Homo sapiens	-
2.7.1.105	H-460 cell	-	Homo sapiens	-
2.7.1.105	HCT-116 cell	-	Homo sapiens	-
2.7.1.105	HCT-116 cell	PFKFB4 is overexpressed in human cancers	Homo sapiens	-
2.7.1.105	leukocyte	-	Homo sapiens	-
2.7.1.105	LNCaP cell	-	Homo sapiens	-
2.7.1.105	LNCaP cell	PFKFB4 is overexpressed in human cancers	Homo sapiens	-
2.7.1.105	lung	-	Homo sapiens	-
2.7.1.105	lung adenocarcinoma cell	overexpression of isozyme PFKFB4. PFKFB4 expression correlates with hypoxia in human lung adenocarcinoma xenografts	Homo sapiens	-
2.7.1.105	MCF-7 cell	-	Homo sapiens	-
2.7.1.105	MCF-7 cell	PFKFB4 is overexpressed in human cancers	Homo sapiens	-
2.7.1.105	additional information	isozyme PFKFB4 tissue expression analysis, overview	Homo sapiens	-
2.7.1.105	NCI-H460 cell	PFKFB4 is overexpressed in human cancers	Homo sapiens	-
2.7.1.105	ovary	-	Homo sapiens	-
2.7.1.105	pancreas	-	Homo sapiens	-
2.7.1.105	PC-3 cell	PFKFB4 is overexpressed in human cancers	Homo sapiens	-
2.7.1.105	placenta	-	Homo sapiens	-
2.7.1.105	prostate	-	Homo sapiens	-
2.7.1.105	skeletal muscle	-	Homo sapiens	-
2.7.1.105	spleen	-	Homo sapiens	-
2.7.1.105	testis	-	Homo sapiens	-
3.1.3.46	A-549 cell	-	Homo sapiens	-
3.1.3.46	colon	-	Homo sapiens	-
3.1.3.46	leukocyte	-	Homo sapiens	-
3.1.3.46	LNCaP cell	-	Homo sapiens	-
3.1.3.46	lung	-	Homo sapiens	-
3.1.3.46	lung adenocarcinoma cell	-	Homo sapiens	-
3.1.3.46	MCF-7 cell	-	Homo sapiens	-
3.1.3.46	NCI-H460 cell	-	Homo sapiens	-
3.1.3.46	ovary	-	Homo sapiens	-
3.1.3.46	pancreas	-	Homo sapiens	-
3.1.3.46	placenta	-	Homo sapiens	-
3.1.3.46	prostate gland	-	Homo sapiens	-
3.1.3.46	skeletal muscle	-	Homo sapiens	-
3.1.3.46	spleen	-	Homo sapiens	-
3.1.3.46	testis	-	Homo sapiens	-

Substrates and Products (Substrate)

EC Number	Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.
2.7.1.105	ATP + beta-D-fructose 6-phosphate	-	Homo sapiens	ADP + beta-D-fructose 2,6-bisphosphate	-	?
2.7.1.105	additional information	recombinant human PFKFB4 kinase activity is 4.3-fold greater than its phosphatase activity	Homo sapiens	?	-	?
3.1.3.46	beta-D-fructose 2,6-bisphosphate + H2O	-	Homo sapiens	D-fructose 6-phosphate + phosphate	-	?

Synonyms

EC Number	Synonyms	Comment	Organism
2.7.1.105	6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4	-	Homo sapiens
2.7.1.105	PFKFB4	-	Homo sapiens
3.1.3.46	6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4	-	Homo sapiens
3.1.3.46	PFKFB4	-	Homo sapiens

Cofactor

EC Number	Cofactor	Comment	Organism	Structure
2.7.1.105	ATP	-	Homo sapiens

Expression

EC Number	Organism	Comment	Expression
2.7.1.105	Homo sapiens	isozyme PFKFB4 is induced by hypoxia	up
3.1.3.46	Homo sapiens	the enzyme isoform PFKFB4 is about 3fold overexpressed in lung adenocarcinoma compared to normal lung tissue. PFKFB4 mRNA and protein expression are also increased by hypoxia	up

General Information

EC Number	General Information	Comment	Organism
2.7.1.105	malfunction	PFKFB4 inhibition in H-460 cells reduces glycolytic flux to lactate and glutamate. PFKFB4 inhibition in H-460 cells increases apoptosis under normoxic and hypoxic conditions	Homo sapiens
2.7.1.105	physiological function	isozyme PFKFB4 expressed in multiple transformed cells and tumors functions to synthesize fructose 2,6-bisphosphate, PFKFB4 is required for cancer cell survival during the metabolic response to hypoxia, presumably to enable glycolytic production of ATP when the electron transport chain is not fully operational. Isozyme PFKFB4 is overexpressed in human cancers, induced by hypoxia and required for survival and growth of several cancer cell lines	Homo sapiens
3.1.3.46	malfunction	knockdown of isoform PFKFB4 reduces tumor growth, glucose uptake and beta-D-fructose 2,6-bisphosphate and increases apoptosis	Homo sapiens
3.1.3.46	physiological function	fructose-2,6-bisphosphate synthesis by 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 is required for the glycolytic response to hypoxia and tumor growth	Homo sapiens