Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

PFKL (P17858) - Overview - Molecular Target Synopsis

Protein


PFKL, ATP-dependent 6-phosphofructokinase, liver type
Enzyme Classification 2.7.1.11
UniProt P17858

Also Known as PFKAL_HUMAN, PFKL

Catalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate by ATP, the first committing step of glycolysis (PubMed:22923583). Negatively regulates the phagocyte oxidative burst in response to bacterial infection by controlling cellular NADPH biosynthesis and NADPH oxidase-derived reactive oxygen species. Upon macrophage activation, drives the metabolic switch toward glycolysis, thus preventing glucose turnover that produces NADPH via pentose phosphate pathway. Homo- and heterotetramers (By similarity). Phosphofructokinase (PFK) enzyme functions as a tetramer composed of different combinations of 3 types of subunits, called PFKM (where M stands for Muscle), PFKL (Liver) and PFKP (Platelet). The composition of the PFK tetramer differs according to the tissue type it is present in. In muscles, it is composed of 4 PFKM subunits (also called M4). In the liver, the predominant form is a tetramer of PFKL subunits (L4). In erythrocytes, both PFKM and PFKL subunits randomly tetramerize to form M4, L4 and other combinations (ML3, M2L2, M3L). The kinetic and regulatory properties of the tetrameric enzyme are dependent on the subunit composition, hence can vary across tissues.

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: PFKL is active in the following subcellular-locations: cytoplasm.
GO terms: PFKL is active in the following subcellular-locations: 6-phosphofructokinase complex, cytosol, extracellular exosome, extracellular region, ficolin-1-rich granule lumen, membrane, secretory granule lumen.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project PFKL has gain in 0 cell-lines, loss in 1 cell-lines and no signal in 1004 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: SNB_75, HS578T, SK_OV_3

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: HM7, G84, NCI-H2595

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, K562, HMEC

(see details)

RNA Interference


PFKL was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: MCF12A, LM7. (see details)

3D Structures


At greater than 50% identity similarity to PFKL there are:
9 structures (33 chains) solved
7 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


PFKL has been screened with compounds ( bioactivities). (see details)