PAK1
entrez
5058
canonical
uniprot
Q13153
canonical
ensembl
ENSG00000149269
resolver
ensp
ENSP00000278568
resolver
ensp
ENSP00000348696
resolver
ensp
ENSP00000433211
resolver
ensp
ENSP00000433423
resolver
ensp
ENSP00000543351
resolver
ensp
ENSP00000543352
resolver
ensp
ENSP00000543353
resolver
ensp
ENSP00000543356
resolver
ensp
ENSP00000543357
resolver
ensp
ENSP00000543359
resolver
ensp
ENSP00000543362
resolver
ensp
ENSP00000543366
resolver
ensp
ENSP00000543367
resolver
ensp
ENSP00000543368
resolver
ensp
ENSP00000543369
resolver
ensp
ENSP00000626857
resolver
ensp
ENSP00000626858
resolver
ensp
ENSP00000626860
resolver
ensp
ENSP00000626863
resolver
ensp
ENSP00000646697
resolver
ensp
ENSP00000646698
resolver
ensp
ENSP00000682489
resolver
ensp
ENSP00000682490
resolver
ensp
ENSP00000682491
resolver
ensp
ENSP00000682492
resolver
ensp
ENSP00000682493
resolver
ensp
ENSP00000682495
resolver
ensp
ENSP00000760148
resolver
enst
ENST00000528203
resolver
enst
ENST00000530617
resolver
genesymbol
PAK1
resolver
hgnc
HGNC:8590
resolver
uniprot
B3KNX7
resolver
uniprot
E9PM17
resolver
uniprot
F6SDP4
resolver
uniprot
O75561
resolver
uniprot
Q13567
resolver
uniprot
Q32M53
resolver
uniprot
Q32M54
resolver
uniprot
Q86W79
resolver
uniprot_entry
B3KNX7_HUMAN
resolver
uniprot_entry
E9PM17_HUMAN
resolver
uniprot_entry
F6SDP4_HUMAN
resolver
uniprot_entry
PAK1_HUMAN
resolver
uniprot_sec
O75561
resolver
uniprot_sec
Q13567
resolver
uniprot_sec
Q32M53
resolver
uniprot_sec
Q32M54
resolver
uniprot_sec
Q86W79
resolver
activity_regulation
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, and enables activation by phosphorylation of Thr-423 (PubMed:10995762, PubMed:11804587, PubMed:15893667, PubMed:9032240). Phosphorylation of Thr-84 by OXSR1 inhibits activation (By similarity). {ECO:0000250|UniProtKB:P35465, ECO:0000269|PubMed:10995762, ECO:0000269|PubMed:11804587, ECO:0000269|PubMed:15893667, ECO:0000269|PubMed:9032240}.
uniprot
proteins
amino_acid_sequence
MSNNGLDIQDKPPAPPMRNTSTMIGAGSKDAGTLNHGSKPLPPNPEEKKKKDRFYRSILPGDKTNKKKEKERPEISLPSDFEHTIHVGFDAVTGEFTGMPEQWARLLQTSNITKSEQKKNPQAVLDVLEFYNSKKTSNSQKYMSFTDKSAEDYNSSNALNVKAVSETPAVPPVSEDEDDDDDDATPPPVIAPRPEHTKSVYTRSVIEPLPVTPTRDVATSPISPTENNTTPPDALTRNTEKQKKKPKMSDEEILEKLRSIVSVGDPKKKYTRFEKIGQGASGTVYTAMDVATGQEVAIKQMNLQQQPKKELIINEILVMRENKNPNIVNYLDSYLVGDELWVVMEYLAGGSLTDVVTETCMDEGQIAAVCRECLQALEFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAQITPEQSKRSTMVGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMIEGEPPYLNENPLRALYLIATNGTPELQNPEKLSAIFRDFLNRCLEMDVEKRGSAKELLQHQFLKIAKPLSSLTPLIAAAKEATKNNH
uniprot
proteins
disease_involvement
DISEASE: Intellectual developmental disorder with macrocephaly, seizures, and speech delay (IDDMSSD) [MIM:618158]: An autosomal dominant neurodevelopmental disorder characterized by impaired intellectual development, poor speech, postnatal macrocephaly, and seizures. {ECO:0000269|PubMed:30290153}. 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: Protein kinase involved in intracellular signaling pathways downstream of integrins and receptor-type kinases that plays an important role in cytoskeleton dynamics, in cell adhesion, migration, proliferation, apoptosis, mitosis, and in vesicle-mediated transport processes (PubMed:10551809, PubMed:11896197, PubMed:12876277, PubMed:14585966, PubMed:15611088, PubMed:17726028, PubMed:17989089, PubMed:30290153, PubMed:17420447). Can directly phosphorylate BAD and protects cells against apoptosis (By similarity). Activated by interaction with CDC42 and RAC1 (PubMed:8805275, PubMed:9528787). Functions as a GTPase effector that links the Rho-related GTPases CDC42 and RAC1 to the JNK MAP kinase pathway (PubMed:8805275, PubMed:9528787). Phosphorylates and activates MAP2K1, and thereby mediates activation of downstream MAP kinases (By similarity). Involved in the reorganization of the actin cytoskeleton, actin stress fibers and of focal adhesion complexes (PubMed:9032240, PubMed:9395435). Phosphorylates the tubulin chaperone TBCB and thereby plays a role in the regulation of microtubule biogenesis and organization of the tubulin cytoskeleton (PubMed:15831477). Plays a role in the regulation of insulin secretion in response to elevated glucose levels (PubMed:22669945). Part of a ternary complex that contains PAK1, DVL1 and MUSK that is important for MUSK-dependent regulation of AChR clustering during the formation of the neuromuscular junction (NMJ) (By similarity). Activity is inhibited in cells undergoing apoptosis, potentially due to binding of CDC2L1 and CDC2L2 (PubMed:12624090). Phosphorylates MYL9/MLC2 (By similarity). Phosphorylates RAF1 at 'Ser-338' and 'Ser-339' resulting in: activation of RAF1, stimulation of RAF1 translocation to mitochondria, phosphorylation of BAD by RAF1, and RAF1 binding to BCL2 (PubMed:11733498). Phosphorylates SNAI1 at 'Ser-246' promoting its transcriptional repressor activity by increasing its accumulation in the nucleus (PubMed:15833848). In podocytes, promotes NR3C2 nuclear localization (By similarity). Required for atypical chemokine receptor ACKR2-induced phosphorylation of LIMK1 and cofilin (CFL1) and for the up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation (PubMed:23633677). In synapses, seems to mediate the regulation of F-actin cluster formation performed by SHANK3, maybe through CFL1 phosphorylation and inactivation (By similarity). Plays a role in RUFY3-mediated facilitating gastric cancer cells migration and invasion (PubMed:25766321). In response to DNA damage, phosphorylates MORC2 which activates its ATPase activity and facilitates chromatin remodeling (PubMed:23260667). In neurons, plays a crucial role in regulating GABA(A) receptor synaptic stability and hence GABAergic inhibitory synaptic transmission through its role in F-actin stabilization (By similarity). In hippocampal neurons, necessary for the formation of dendritic spines and excitatory synapses; this function is dependent on kinase activity and may be exerted by the regulation of actomyosin contractility through the phosphorylation of myosin II regulatory light chain (MLC) (By similarity). Along with GIT1, positively regulates microtubule nucleation during interphase (PubMed:27012601). Phosphorylates FXR1, promoting its localization to stress granules and activity (PubMed:20417602). Phosphorylates ILK on 'Thr-173' and 'Ser-246', promoting nuclear export of ILK (PubMed:17420447). {ECO:0000250|UniProtKB:O88643, ECO:0000250|UniProtKB:P35465, ECO:0000269|PubMed:10551809, ECO:0000269|PubMed:11733498, ECO:0000269|PubMed:11896197, ECO:0000269|PubMed:12624090, ECO:0000269|PubMed:12876277, ECO:0000269|PubMed:14585966, ECO:0000269|PubMed:15611088, ECO:0000269|PubMed:15831477, ECO:0000269|PubMed:15833848, ECO:0000269|PubMed:17420447, ECO:0000269|PubMed:17726028, ECO:0000269|PubMed:17989089, ECO:0000269|PubMed:20417602, ECO:0000269|PubMed:22669945, ECO:0000269|PubMed:23260667, ECO:0000269|PubMed:23633677, ECO:0000269|PubMed:25766321, ECO:0000269|PubMed:27012601, ECO:0000269|PubMed:30290153, ECO:0000269|PubMed:8805275, ECO:0000269|PubMed:9032240, ECO:0000269|PubMed:9395435, ECO:0000269|PubMed:9528787}.
uniprot
proteins
mass_dalton
60647
uniprot
proteins
mutagenesis
MUTAGEN 83; /note="H->L: Abolishes interaction with CDC42, leading to strongly decreased activity; when associated with L-86."; /evidence="ECO:0000269|PubMed:10551809, ECO:0000269|PubMed:9774440"; MUTAGEN 86; /note="H->L: Abolishes interaction with CDC42, leading to strongly decreased activity; when associated with L-83."; /evidence="ECO:0000269|PubMed:10551809, ECO:0000269|PubMed:9774440"; MUTAGEN 107; /note="L->F: Abolishes autoinhibition, leading to constitutive kinase activity."; /evidence="ECO:0000269|PubMed:10551809"; MUTAGEN 299; /note="K->R: Strongly decreases activity. Abolishes kinase activity; when associated with N-389."; /evidence="ECO:0000269|PubMed:22153498"; MUTAGEN 389; /note="D->N: Abolishes kinase activity; when associated with R-299."; /evidence="ECO:0000269|PubMed:22153498"; MUTAGEN 393; /note="D->A: Abolishes autophosphorylation at Thr-423."; /evidence="ECO:0000269|PubMed:22153498"; MUTAGEN 423; /note="T->A: Decreases CDC42-stimulated activity and autophosphorylation."; /evidence="ECO:0000269|PubMed:10551809"; MUTAGEN 423; /note="T->E: Constitutive kinase activity."; /evidence="ECO:0000269|PubMed:10551809
uniprot
proteins
post_translational_modification
PTM: Autophosphorylated in trans, meaning that in a dimer, one kinase molecule phosphorylates the other one (PubMed:20417602, PubMed:22153498, PubMed:23633677). Activated by autophosphorylation at Thr-423 in response to a conformation change, triggered by interaction with GTP-bound CDC42 or RAC1 (PubMed:10551809). Activated by phosphorylation at Thr-423 by BRSK2 and by PDPK1 (PubMed:10995762, PubMed:22669945). Phosphorylated by JAK2 in response to PRL; this increases PAK1 kinase activity. Phosphorylated at Ser-21 by PKB/AKT; this reduces interaction with NCK1 and association with focal adhesion sites (PubMed:14585966). Upon DNA damage, phosphorylated at Thr-212 and translocates to the nucleoplasm (PubMed:23260667). Phosphorylated at tyrosine residues, which can be enhanced by NTN1 (By similarity). {ECO:0000250|UniProtKB:O88643, ECO:0000269|PubMed:10551809, ECO:0000269|PubMed:10995762, ECO:0000269|PubMed:14585966, ECO:0000269|PubMed:20417602, ECO:0000269|PubMed:22153498, ECO:0000269|PubMed:22669945, ECO:0000269|PubMed:23260667, ECO:0000269|PubMed:23633677}.
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
10026169
uniprot
proteins
pubmed
10551809
uniprot
proteins
pubmed
10975528
uniprot
proteins
pubmed
10995762
uniprot
proteins
pubmed
11733498
uniprot
proteins
pubmed
11804587
uniprot
proteins
pubmed
11896197
uniprot
proteins
pubmed
12624090
uniprot
proteins
pubmed
12876277
uniprot
proteins
pubmed
14585966
uniprot
proteins
pubmed
15169762
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15611088
uniprot
proteins
pubmed
15831477
uniprot
proteins
pubmed
15833848
uniprot
proteins
pubmed
15893667
uniprot
proteins
pubmed
16061695
uniprot
proteins
pubmed
16101281
uniprot
proteins
pubmed
16278681
uniprot
proteins
pubmed
16554811
uniprot
proteins
pubmed
16964243
uniprot
proteins
pubmed
17420447
uniprot
proteins
pubmed
17726028
uniprot
proteins
pubmed
17989089
uniprot
proteins
pubmed
18325335
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18716323
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20417602
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
22153498
uniprot
proteins
pubmed
22669945
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23260667
uniprot
proteins
pubmed
23503467
uniprot
proteins
pubmed
23633677
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
25766321
uniprot
proteins
pubmed
26048998
uniprot
proteins
pubmed
26598620
uniprot
proteins
pubmed
26940976
uniprot
proteins
pubmed
27012601
uniprot
proteins
pubmed
30290153
uniprot
proteins
pubmed
8805275
uniprot
proteins
pubmed
9032240
uniprot
proteins
pubmed
9395435
uniprot
proteins
pubmed
9528787
uniprot
proteins
pubmed
9774440
uniprot
proteins
sequence_length
545
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11896197, ECO:0000269|PubMed:23260667, ECO:0000269|PubMed:25766321}. Cell junction, focal adhesion {ECO:0000269|PubMed:11896197, ECO:0000269|PubMed:25766321}. Cell projection, lamellipodium {ECO:0000269|PubMed:11896197}. Cell membrane {ECO:0000269|PubMed:25766321}. Cell projection, ruffle membrane {ECO:0000269|PubMed:25766321}. Cell projection, invadopodium {ECO:0000269|PubMed:25766321}. Nucleus, nucleoplasm {ECO:0000269|PubMed:23260667}. Chromosome {ECO:0000269|PubMed:23260667}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:27012601}. Note=Colocalizes with RUFY3, F-actin and other core migration components in invadopodia at the cell periphery (PubMed:25766321). Recruited to the cell membrane by interaction with CDC42 and RAC1. Recruited to focal adhesions upon activation. Colocalized with CIB1 within membrane ruffles during cell spreading upon readhesion to fibronectin. Upon DNA damage, translocates to the nucleoplasm when phosphorylated at Thr-212 where is co-recruited with MORC2 on damaged chromatin (PubMed:23260667). Localization to the centrosome does not depend upon the presence of gamma-tubulin (PubMed:27012601). Localization of the active, but not inactive, protein to the adhesions and edge of lamellipodia is mediated by interaction with GIT1 (PubMed:11896197). {ECO:0000250|UniProtKB:P35465, ECO:0000269|PubMed:11896197, ECO:0000269|PubMed:23260667, ECO:0000269|PubMed:25766321, ECO:0000269|PubMed:27012601}.
uniprot
proteins