| Predicate | Object |
|---|---|
| rdf:type | |
| biopax3:comment |
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. 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. GENE SYNONYMS:PAK2. COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License.,
SEQUENCE 524 AA; 58043 MW; 00A7CD15F93D4180 CRC64;
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| biopax3:xref | |
| biopax3:displayName |
PAK2_HUMAN
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| biopax3:name |
2.7.11.1,
C-t-PAK2,
Gamma-PAK,
PAK-2,
PAK-2p27,
PAK-2p34,
PAK2,
PAK65,
S6/H4 kinase,
p21-activated kinase 2,
p27,
p34,
p58
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| biopax3:entityFeature |
urn:biopax:ModificationFeature:PAK2_HUMAN_1,
urn:biopax:ModificationFeature:PAK2_HUMAN_10,
urn:biopax:ModificationFeature:PAK2_HUMAN_11,
urn:biopax:ModificationFeature:PAK2_HUMAN_12,
urn:biopax:ModificationFeature:PAK2_HUMAN_2,
urn:biopax:ModificationFeature:PAK2_HUMAN_3,
urn:biopax:ModificationFeature:PAK2_HUMAN_4,
urn:biopax:ModificationFeature:PAK2_HUMAN_5,
urn:biopax:ModificationFeature:PAK2_HUMAN_6,
urn:biopax:ModificationFeature:PAK2_HUMAN_7,
urn:biopax:ModificationFeature:PAK2_HUMAN_8,
urn:biopax:ModificationFeature:PAK2_HUMAN_9
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| biopax3:organism | |
| biopax3:sequence |
MSDNGELEDKPPAPPVRMSSTIFSTGGKDPLSANHSLKPLPSVPEEKKPRHKIISIFSGTEKGSKKKEKERPEISPPSDFEHTIHVGFDAVTGEFTGMPEQWARLLQTSNITKLEQKKNPQAVLDVLKFYDSNTVKQKYLSFTPPEKDGFPSGTPALNAKGTEAPAVVTEEEDDDEETAPPVIAPRPDHTKSIYTRSVIDPVPAPVGDSHVDGAAKSLDKQKKKTKMTDEEIMEKLRTIVSIGDPKKKYTRYEKIGQGASGTVFTATDVALGQEVAIKQINLQKQPKKELIINEILVMKELKNPNIVNFLDSYLVGDELFVVMEYLAGGSLTDVVTETCMDEAQIAAVCRECLQALEFLHANQVIHRDIKSDNVLLGMEGSVKLTDFGFCAQITPEQSKRSTMVGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNENPLRALYLIATNGTPELQNPEKLSPIFRDFLNRCLEMDVEKRGSAKELLQHPFLKLAKPLSSLTPLIMAAKEAMKSNR
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| biopax3:standardName |
Serine/threonine-protein kinase PAK 2
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