InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PAK2

Summary

InnateDB Protein

IDBP-71335.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

PAK2

Protein Name

p21 protein (Cdc42/Rac)-activated kinase 2

Synonyms

PAK65; PAKgamma;

Species

Homo sapiens

Ensembl Protein

ENSP00000314067

InnateDB Gene

IDBG-71333 (PAK2)

Protein Structure

UniProt Annotation

Function

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. {ECO:0000269PubMed:12853446, ECO:0000269PubMed:15234964, ECO:0000269PubMed:16617111, ECO:0000269PubMed:19923322, ECO:0000269PubMed:21177766, ECO:0000269PubMed:21317288, ECO:0000269PubMed:21724829, ECO:0000269PubMed:9171063}.

Subcellular Localization

Serine/threonine-protein kinase PAK 2: Cytoplasm. Note=MYO18A mediates the cellular distribution of the PAK2-ARHGEF7-GIT1 complex to the inner surface of the cell membrane.PAK-2p34: Nucleus. Cytoplasm, perinuclear region. Membrane; Lipid-anchor. Note=Interaction with ARHGAP10 probably changes PAK-2p34 location to cytoplasmic perinuclear region. Myristoylation changes PAK-2p34 location to the membrane.

Disease Associations

Tissue Specificity

Ubiquitously expressed. Higher levels seen in skeletal muscle, ovary, thymus and spleen.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 92 experimentally validated interaction(s) in this database.
They are also associated with 3 interaction(s) predicted by orthology.

Experimentally validated
Total	92 [view]
Protein-Protein	91 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	3 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0019901	protein kinase binding
GO:0030296	protein tyrosine kinase activator activity
GO:0042802	identical protein binding

Biological Process

GO:0006468	protein phosphorylation
GO:0006469	negative regulation of protein kinase activity
GO:0006915	apoptotic process
GO:0006921	cellular component disassembly involved in execution phase of apoptosis
GO:0007015	actin filament organization
GO:0007165	signal transduction
GO:0007411	axon guidance
GO:0016032	viral process
GO:0016310	phosphorylation
GO:0018105	peptidyl-serine phosphorylation
GO:0023014	signal transduction by phosphorylation
GO:0031295	T cell costimulation
GO:0038095	Fc-epsilon receptor signaling pathway
GO:0040008	regulation of growth
GO:0042981	regulation of apoptotic process
GO:0043066	negative regulation of apoptotic process
GO:0045087	innate immune response
GO:0046777	protein autophosphorylation
GO:0050690	regulation of defense response to virus by virus
GO:0050731	positive regulation of peptidyl-tyrosine phosphorylation
GO:0050852	T cell receptor signaling pathway
GO:0061098	positive regulation of protein tyrosine kinase activity
GO:2001238	positive regulation of extrinsic apoptotic signaling pathway
GO:2001271	negative regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0048471	perinuclear region of cytoplasm

Protein Structure and Domains

PDB ID

InterPro

IPR000095 CRIB domain
IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR011026 Wiscott-Aldrich syndrome protein, C-terminal
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00786
PF00069
PF07714

PRINTS

PR00109

PIRSF

SMART

SM00285
SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt