Literature summary for 2.7.1.105 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

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

Protein Variants	Comment	Organism
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	Comment	Organism	Structure
Mg2+	required	Homo sapiens

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

Organism	UniProt	Comment	Textmining
Homo sapiens	Q16877	gene/isozyme Pfkfb4	-

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

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

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

Cofactor	Comment	Organism	Structure
ATP	-	Homo sapiens

Organism	Comment	Expression
Homo sapiens	isozyme PFKFB4 is induced by hypoxia	up

General Information	Comment	Organism
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
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