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

PAK4 (O96013) - Overview - Molecular Target Synopsis

Protein


PAK4, Serine/threonine-protein kinase PAK 4
Enzyme Classification 2.7.11.1
UniProt O96013

Also Known as PAK4_HUMAN, PAK4, KIAA1142

Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell migration, growth, proliferation or cell survival. Activation by various effectors including growth factor receptors or active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates and inactivates the protein phosphatase SSH1, leading to increased inhibitory phosphorylation of the actin binding/depolymerizing factor cofilin. Decreased cofilin activity may lead to stabilization of actin filaments. Phosphorylates LIMK1, a kinase that also inhibits the activity of cofilin. Phosphorylates integrin beta5/ITGB5 and thus regulates cell motility. Phosphorylates ARHGEF2 and activates the downstream target RHOA that plays a role in the regulation of assembly of focal adhesions and actin stress fibers. Stimulates cell survival by phosphorylating the BCL2 antagonist of cell death BAD. Alternatively, inhibits apoptosis by preventing caspase-8 binding to death domain receptors in a kinase independent manner. Plays a role in cell-cycle progression by controlling levels of the cell-cycle regulatory protein CDKN1A and by phosphorylating RAN. Interacts with FGFR2 and GRB2 (By similarity). Interacts tightly with GTP-bound but not GDP-bound CDC42/p21 and weakly with RAC1 (PubMed:15827085). Interacts with INKA1 (PubMed:26607847). Interacts with SH3RF2 (PubMed:24130170).

5ZJW
CRYSTAL STRUCTURE OF PAK4 IN COMPLEX WITH INHIBITOR CZG353
RCSB/PDB
Inspect Structure
See all 3D Structures for PAK4

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: PAK4 is active in the following subcellular-locations: cytoplasm.
GO terms: PAK4 is active in the following subcellular-locations: cell-cell adherens junction, cytoplasm, focal adhesion, Golgi apparatus.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project PAK4 has gain in 10 cell-lines, loss in 1 cell-lines and no signal in 994 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: OVCAR_3, A549, HOP_62

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: NIH:OVCAR-3, KLE, PANC-1

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: A549, HUVEC, IMR-90

(see details)

RNA Interference


PAK4 was reported in the following RNAI studies:

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

3D Structures


For PAK4 there are:
35 structures (51 chains) solved
22 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


PAK4 has been screened with 898 compounds (1351 bioactivities), 118 compounds have bioactivities that show binding affinity of <= 500nM (180 bioactivities). (see details)