PAK2
entrez
5062
canonical
uniprot
Q13177
canonical
ensembl
ENSG00000180370
resolver
ensp
ENSP00000314067
resolver
ensp
ENSP00000541447
resolver
ensp
ENSP00000541450
resolver
ensp
ENSP00000629996
resolver
enst
ENST00000327134
resolver
enst
ENST00000871388
resolver
enst
ENST00000871391
resolver
enst
ENST00000959937
resolver
genesymbol
PAK2
resolver
hgnc
HGNC:8591
resolver
uniprot
A8K5M4
resolver
uniprot
Q13154
resolver
uniprot
Q6ISC3
resolver
uniprot_entry
A8K5M4_HUMAN
resolver
uniprot_entry
PAK2_HUMAN
resolver
uniprot_sec
Q13154
resolver
uniprot_sec
Q6ISC3
resolver
activity_regulation
ACTIVITY REGULATION: Activated by binding small G proteins (By similarity). 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, autophosphorylated PAK-2p34 is constitutively active (PubMed:9786869). {ECO:0000250|UniProtKB:Q13153, ECO:0000269|PubMed:9786869}.
uniprot
proteins
amino_acid_sequence
MSDNGELEDKPPAPPVRMSSTIFSTGGKDPLSANHSLKPLPSVPEEKKPRHKIISIFSGTEKGSKKKEKERPEISPPSDFEHTIHVGFDAVTGEFTGMPEQWARLLQTSNITKLEQKKNPQAVLDVLKFYDSNTVKQKYLSFTPPEKDGFPSGTPALNAKGTEAPAVVTEEEDDDEETAPPVIAPRPDHTKSIYTRSVIDPVPAPVGDSHVDGAAKSLDKQKKKTKMTDEEIMEKLRTIVSIGDPKKKYTRYEKIGQGASGTVFTATDVALGQEVAIKQINLQKQPKKELIINEILVMKELKNPNIVNFLDSYLVGDELFVVMEYLAGGSLTDVVTETCMDEAQIAAVCRECLQALEFLHANQVIHRDIKSDNVLLGMEGSVKLTDFGFCAQITPEQSKRSTMVGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNENPLRALYLIATNGTPELQNPEKLSPIFRDFLNRCLEMDVEKRGSAKELLQHPFLKLAKPLSSLTPLIMAAKEAMKSNR
uniprot
proteins
disease_involvement
DISEASE: Knobloch syndrome 2 (KNO2) [MIM:618458]: An autosomal dominant form of Knobloch syndrome characterized by high myopia, vitreoretinal degeneration, retinal detachment, occipital encephalocele or scalp lesions, and mild to severe psychomotor delay. {ECO:0000269|PubMed:33693784}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.7.11.1
uniprot
proteins
function
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 (PubMed:12853446, PubMed:16617111, PubMed:19273597, PubMed:19923322, PubMed:33693784, PubMed:7744004, PubMed:9171063). Acts as a downstream effector of the small GTPases CDC42 and RAC1 (PubMed:7744004). 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 (PubMed:7744004). Full-length PAK2 stimulates cell survival and cell growth (PubMed:7744004). Phosphorylates MAPK4 and MAPK6 and activates the downstream target MAPKAPK5, a regulator of F-actin polymerization and cell migration (PubMed:21317288). Phosphorylates JUN and plays an important role in EGF-induced cell proliferation (PubMed:21177766). Phosphorylates many other substrates including histone H4 to promote assembly of H3.3 and H4 into nucleosomes, BAD, ribosomal protein S6, or MBP (PubMed:21724829). Phosphorylates CASP7, thereby preventing its activity (PubMed:21555521, PubMed:27889207). Additionally, associates with ARHGEF7 and GIT1 to perform kinase-independent functions such as spindle orientation control during mitosis (PubMed:19273597, PubMed:19923322). 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 (PubMed:12853446, PubMed:16617111, PubMed:9171063). Caspase-activated PAK2 phosphorylates MKNK1 and reduces cellular translation (PubMed:15234964). {ECO:0000269|PubMed:12853446, ECO:0000269|PubMed:15234964, ECO:0000269|PubMed:16617111, ECO:0000269|PubMed:19273597, ECO:0000269|PubMed:19923322, ECO:0000269|PubMed:21177766, ECO:0000269|PubMed:21317288, ECO:0000269|PubMed:21555521, ECO:0000269|PubMed:21724829, ECO:0000269|PubMed:27889207, ECO:0000269|PubMed:33693784, ECO:0000269|PubMed:7744004, ECO:0000269|PubMed:9171063}.
uniprot
proteins
mass_dalton
58043
uniprot
proteins
mutagenesis
MUTAGEN 212; /note="D->N: Inhibits caspase-mediated cleavage."; /evidence="ECO:0000269|PubMed:9171063"; MUTAGEN 213; /note="G->A: Abolishes myristoylation of PAK-2p34 and membrane location."; /evidence="ECO:0000269|PubMed:16617111"; MUTAGEN 239..243; /note="IVSIG->REGRS: Abolishes nuclear export."; /evidence="ECO:0000269|PubMed:12853446"; MUTAGEN 246..248; /note="KKK->MHE: Greatly inhibits nuclear localization."; /evidence="ECO:0000269|PubMed:12853446"; MUTAGEN 278; /note="K->R: Abolishes kinase activity and autophosphorylation."; /evidence="ECO:0000269|PubMed:9786869"; MUTAGEN 402; /note="T->A: Abolishes kinase activity and greatly inhibits autophosphorylation of PAK-2p27 and PAK-2p34."; /evidence="ECO:0000269|PubMed:9786869
uniprot
proteins
post_translational_modification
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. {ECO:0000269|PubMed:21098037, ECO:0000269|PubMed:7673144, ECO:0000269|PubMed:9786869}.; PTM: During apoptosis proteolytically cleaved by caspase-3 or caspase-3-like proteases to yield active PAK-2p34. {ECO:0000269|PubMed:12853446, ECO:0000269|PubMed:9171063, ECO:0000269|PubMed:9786869}.; PTM: Ubiquitinated, leading to its proteasomal degradation. {ECO:0000269|PubMed:12853446}.; PTM: [PAK-2p34]: PAK-2p34 is myristoylated. {ECO:0000269|PubMed:16617111}.
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
STE Ser/Thr protein kinase family
uniprot
proteins
protein_family
STE20 subfamily
uniprot
proteins
pubmed
11070003
uniprot
proteins
pubmed
12853446
uniprot
proteins
pubmed
15234964
uniprot
proteins
pubmed
15471851
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16374509
uniprot
proteins
pubmed
16617111
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
18088087
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18716323
uniprot
proteins
pubmed
19273597
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
19923322
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20696164
uniprot
proteins
pubmed
21098037
uniprot
proteins
pubmed
21170023
uniprot
proteins
pubmed
21177766
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21317288
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
21555521
uniprot
proteins
pubmed
21724829
uniprot
proteins
pubmed
22223895
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
27889207
uniprot
proteins
pubmed
33693784
uniprot
proteins
pubmed
7556080
uniprot
proteins
pubmed
7673144
uniprot
proteins
pubmed
7744004
uniprot
proteins
pubmed
9171063
uniprot
proteins
pubmed
9786869
uniprot
proteins
sequence_length
524
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Serine/threonine-protein kinase PAK 2]: Cytoplasm {ECO:0000269|PubMed:19923322, ECO:0000269|PubMed:21555521}. Nucleus {ECO:0000269|PubMed:12853446, ECO:0000269|PubMed:21555521}. Note=MYO18A mediates the cellular distribution of the PAK2-ARHGEF7-GIT1 complex to the inner surface of the cell membrane. {ECO:0000269|PubMed:19923322}.; SUBCELLULAR LOCATION: [PAK-2p34]: Nucleus {ECO:0000269|PubMed:12853446}. Cytoplasm, perinuclear region {ECO:0000269|PubMed:15471851}. Membrane {ECO:0000269|PubMed:16617111}; Lipid-anchor {ECO:0000269|PubMed:16617111}. Note=Interaction with ARHGAP10 probably changes PAK-2p34 location to cytoplasmic perinuclear region (PubMed:15471851). Myristoylation changes PAK-2p34 location to the membrane (PubMed:16617111). {ECO:0000269|PubMed:15471851, ECO:0000269|PubMed:16617111}.
uniprot
proteins