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

PAK2 (Q13177) - Overview - Molecular Target Synopsis

Protein


PAK2, Serine/threonine-protein kinase PAK 2
Enzyme Classification 2.7.11.1
UniProt Q13177

Also Known as PAK2_HUMAN, PAK2

Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell motility, cell cycle progression, apoptosis or proliferation. Acts as downstream effector of the small GTPases CDC42 and RAC1. Activation by the binding of active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Full-length PAK2 stimulates cell survival and cell growth. Phosphorylates MAPK4 and MAPK6 and activates the downstream target MAPKAPK5, a regulator of F-actin polymerization and cell migration. Phosphorylates JUN and plays an important role in EGF-induced cell proliferation. Phosphorylates many other substrates including histone H4 to promote assembly of H3.3 and H4 into nucleosomes, BAD, ribosomal protein S6, or MBP. Additionally, associates with ARHGEF7 and GIT1 to perform kinase-independent functions such as spindle orientation control during mitosis. On the other hand, apoptotic stimuli such as DNA damage lead to caspase-mediated cleavage of PAK2, generating PAK-2p34, an active p34 fragment that translocates to the nucleus and promotes cellular apoptosis involving the JNK signaling pathway. Caspase-activated PAK2 phosphorylates MKNK1 and reduces cellular translation. Interacts tightly with GTP-bound but not GDP-bound CDC42/p21 and RAC1. Interacts with SH3MD4. Interacts with SCRIB. Interacts with ARHGEF7 and GIT1. PAK-2p34 interacts with ARHGAP10 (PubMed:15471851, PubMed:16374509, PubMed:18716323, PubMed:19273597). Interacts with RAC1 (PubMed:20696164).

3PCS
14 RESIDUE FRAGMENT OF
SERINE/THREONINE-PROTEIN KINASE PAK 2
IN THE STRUCTURE OF
STRUCTURE OF ESPG-PAK2 AUTOINHIBITORY IALPHA3 HELIX COMPLEX
RCSB/PDB
Inspect Structure
See all 3D Structures for PAK2

Isoforms / Transcripts (Protein Coding)


Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform
524ENSG00000180370ENST00000327134ENSP00000314067Q13177-1
215ENSG00000180370ENST00000426668ENSP00000402927

Sub-cellular localization


UniProt: PAK2 is active in the following subcellular-locations: cytoplasm, membrane, nucleus, perinuclear region.
GO terms: PAK2 is active in the following subcellular-locations: cytoplasm, cytosol, glutamatergic synapse, nucleus, perinuclear region of cytoplasm, plasma membrane, postsynaptic density.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project PAK2 has gain in 7 cell-lines, loss in 1 cell-lines and no signal in 997 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: T47D, OVCAR_5, HS578T

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: PANC-1, WSU-FSCCL, SU-DHL-16

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: NHLF, HSMM, MCF-7

(see details)

RNA Interference


PAK2 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: ASPC1, COV504. (see details)

3D Structures


For PAK2 there are:
1 structures (4 chains) solved
0 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


PAK2 has been screened with 852 compounds (1468 bioactivities), 20 compounds have bioactivities that show binding affinity of <= 500nM (25 bioactivities). (see details)