ID:PAK2_HUMAN DESCRIPTION: RecName: Full=Serine/threonine-protein kinase PAK 2; EC=2.7.11.1; AltName: Full=Gamma-PAK; AltName: Full=PAK65; AltName: Full=S6/H4 kinase; AltName: Full=p21-activated kinase 2; Short=PAK-2; AltName: Full=p58; Contains: RecName: Full=PAK-2p27; Short=p27; Contains: RecName: Full=PAK-2p34; Short=p34; AltName: Full=C-t-PAK2; 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. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. ENZYME REGULATION: Activated by binding small G proteins. Binding of GTP-bound CDC42 or RAC1 to the autoregulatory region releases monomers from the autoinhibited dimer, enables phosphorylation of Thr-402 and allows the kinase domain to adopt an active structure (By similarity). Following caspase cleavage, autophosphorylted PAK-2p34 is constitutively active. SUBUNIT: Interacts tightly with GTP-bound but not GDP-bound CDC42/p21 and RAC1. Interacts with SH3MD4. Interacts with and activated by HIV-1 Nef. Interacts with SCRIB. Interacts with ARHGEF7 and GIT1. PAK-2p34 interacts with ARHGAP10. INTERACTION: Self; NbExp=3; IntAct=EBI-1045887, EBI-1045887; P55210:CASP7; NbExp=6; IntAct=EBI-1045887, EBI-523958; P42858:HTT; NbExp=2; IntAct=EBI-1045887, EBI-466029; P53667:LIMK1; NbExp=2; IntAct=EBI-1045887, EBI-444403; P04049:RAF1; NbExp=2; IntAct=EBI-1045887, EBI-365996; SUBCELLULAR LOCATION: 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. SUBCELLULAR LOCATION: 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. TISSUE SPECIFICITY: Ubiquitously expressed. Higher levels seen in skeletal muscle, ovary, thymus and spleen. PTM: Full length PAK2 is autophosphorylated when activated by CDC42/p21. Following cleavage, both peptides, PAK-2p27 and PAK- 2p34, become highly autophosphorylated, with PAK-2p27 being phosphorylated on serine and PAK-2p34 on threonine residues, respectively. Autophosphorylation of PAK-2p27 can occur in the absence of any effectors and is dependent on phosphorylation of Thr-402, because PAK-2p27 is acting as an exogenous substrate. PTM: During apoptosis proteolytically cleaved by caspase-3 or caspase-3-like proteases to yield active PAK-2p34. PTM: Ubiquitinated, leading to its proteasomal degradation. PTM: PAK-2p34 is myristoylated. SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily. SIMILARITY: Contains 1 CRIB domain. SIMILARITY: Contains 1 protein kinase domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q13177
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0002223 stimulatory C-type lectin receptor signaling pathway GO:0006468 protein phosphorylation GO:0006469 negative regulation of protein kinase activity GO:0006915 apoptotic process GO:0007165 signal transduction GO:0007266 Rho protein signal transduction GO:0007346 regulation of mitotic cell cycle GO:0008152 metabolic process GO:0016032 viral process GO:0016310 phosphorylation GO:0016477 cell migration GO:0018105 peptidyl-serine phosphorylation GO:0023014 signal transduction by protein phosphorylation GO:0030036 actin cytoskeleton organization GO:0031098 stress-activated protein kinase signaling cascade GO:0031295 T cell costimulation GO:0035722 interleukin-12-mediated signaling pathway 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:0043408 regulation of MAPK cascade GO:0046777 protein autophosphorylation GO:0048010 vascular endothelial growth factor receptor signaling pathway 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:0060996 dendritic spine development GO:0061098 positive regulation of protein tyrosine kinase activity GO:0071407 cellular response to organic cyclic compound GO:2001238 positive regulation of extrinsic apoptotic signaling pathway GO:2001271 negative regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis
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Common Gene Haplotype Alleles 
