BioPAX pathway converted from "Ubiquitination of PAK-2p34" in the Reactome database.6.3.2.19Ubiquitination of PAK-2p34Ubiquitination of PAK-2p34PAK-2p34 is ubiquitinated prior to degradation (Jakobi et al., 2003). Here, ubiquitination of PAK-2p34 is described as occurring in the cytosol. However, to date it is not known whether this occurs in the nucleus or in the cytoplasm. Evidence for this reaction comes from experiments using both human and rabbit proteins. The polyubiquitin synthesized in the reaction is inferred to contain lysine-48 (K48) linkages because the modified protein is targeted to the proteasome (Komander 2009).Authored: Jakobi, R, 2008-02-05 11:04:14Reviewed: Chang, E, 2008-05-21 00:05:41Edited: Matthews, L, 2008-02-03 20:50:13Edited: Matthews, L, 2008-05-23 07:17:49Reactome DB_ID: 2116411cytosolGO0005829UniProt:Q29502 PAK2PAK2PAK2FUNCTION 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 (By similarity).ACTIVITY 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. Following caspase cleavage, autophosphorylated PAK-2p34 is constitutively active (By similarity).SUBUNIT 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. Interacts with RAC1 (By similarity).PTM Full-length PAK2 is autophosphorylated when activated by CDC42/p21. Following cleavage, both peptides, PAK-2p27 and PAK-2p34, become highly autophosphorylated. 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 (By similarity).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.Reactomehttp://www.reactome.orgOryctolagus cuniculusNCBI Taxonomy9986UniProtQ29502O-phospho-L-threonine at 402402EQUALO-phospho-L-threonine [MOD:00047]Chain Coordinates213EQUAL524EQUALConverted from EntitySet in ReactomeReactome DB_ID: 1135951Ub [cytosol]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityUBC(457-532) [cytosol]UBB(77-152) [cytosol]UBC(229-304) [cytosol]UBC(609-684) [cytosol]UBC(381-456) [cytosol]UBB(1-76) [cytosol]UBC(153-228) [cytosol]UBA52(1-76) [cytosol]UBB(153-228) [cytosol]UBC(533-608) [cytosol]UBC(77-152) [cytosol]RPS27A(1-76) [cytosol]UBC(305-380) [cytosol]UBC(1-76) [cytosol]Homo sapiensNCBI Taxonomy9606UniProtP0CG48UniProtP0CG47UniProtP62987UniProtP62979Reactome DB_ID: 30958721O-phospho-L-threonine at 402402EQUALubiquitinylated lysine (K48polyUb [cytosol]) at unknown positionubiquitinylated lysine [MOD:01148]213EQUAL524EQUALPHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 69593Ubiquitin ligase [cytosol]Ubiquitin ligaseGO0004842GO molecular functionReactome Database ID Release 7669594Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=69594Reactome Database ID Release 76212920Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=212920ReactomeR-NUL-2129201Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-NUL-212920.112853446Pubmed2003Caspase-activated PAK-2 is regulated by subcellular targeting and proteasomal degradationJakobi, RMcCarthy, CCKoeppel, MAStringer, DKJ Biol Chem 278:38675-8519754430Pubmed2009The emerging complexity of protein ubiquitinationKomander, DavidBiochem. Soc. Trans. 37:937-53