PAK1_MOUSE
ID PAK1_MOUSE Reviewed; 545 AA.
AC O88643;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=Serine/threonine-protein kinase PAK 1 {ECO:0000305};
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:Q13153};
DE AltName: Full=Alpha-PAK {ECO:0000250|UniProtKB:Q13153};
DE AltName: Full=CDC42/RAC effector kinase PAK-A;
DE AltName: Full=p21-activated kinase 1 {ECO:0000250|UniProtKB:Q13153};
DE Short=PAK-1;
DE AltName: Full=p65-PAK {ECO:0000250|UniProtKB:P35465};
GN Name=Pak1 {ECO:0000312|MGI:MGI:1339975}; Synonyms=Paka;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10352232; DOI=10.1016/s0378-1119(99)00110-9;
RA Burbelo P.D., Kozak C.A., Finegold A.A., Hall A., Pirone D.M.;
RT "Cloning, central nervous system expression and chromosomal mapping of the
RT mouse PAK-1 and PAK-3 genes.";
RL Gene 232:209-215(1999).
RN [2]
RP PROTEIN SEQUENCE OF 204-215; 276-299; 309-320; 372-388 AND 472-489, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=OF1; TISSUE=Hippocampus;
RA Lubec G., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [3]
RP FUNCTION.
RX PubMed=10611223; DOI=10.1128/mcb.20.2.453-461.2000;
RA Schurmann A., Mooney A.F., Sanders L.C., Sells M.A., Wang H.G., Reed J.C.,
RA Bokoch G.M.;
RT "p21-activated kinase 1 phosphorylates the death agonist bad and protects
RT cells from apoptosis.";
RL Mol. Cell. Biol. 20:453-461(2000).
RN [4]
RP FUNCTION, AND PHOSPHORYLATION AT THR-212.
RX PubMed=12176334; DOI=10.1016/s0960-9822(02)00956-9;
RA Banerjee M., Worth D., Prowse D.M., Nikolic M.;
RT "Pak1 phosphorylation on T212 affects microtubules in cells undergoing
RT mitosis.";
RL Curr. Biol. 12:1233-1239(2002).
RN [5]
RP FUNCTION IN NEUROMUSCULAR JUNCTION DEVELOPMENT, AND INTERACTION WITH DVL1
RP AND MUSK.
RX PubMed=12165471; DOI=10.1016/s0896-6273(02)00783-3;
RA Luo Z.G., Wang Q., Zhou J.Z., Wang J., Luo Z., Liu M., He X.,
RA Wynshaw-Boris A., Xiong W.C., Lu B., Mei L.;
RT "Regulation of AChR clustering by Dishevelled interacting with MuSK and
RT PAK1.";
RL Neuron 35:489-505(2002).
RN [6]
RP INTERACTION WITH NISCH.
RX PubMed=15229651; DOI=10.1038/sj.emboj.7600291;
RA Alahari S.K., Reddig P.J., Juliano R.L.;
RT "The integrin-binding protein Nischarin regulates cell migration by
RT inhibiting PAK.";
RL EMBO J. 23:2777-2788(2004).
RN [7]
RP INTERACTION WITH DSCAM.
RX PubMed=15169762; DOI=10.1074/jbc.m401878200;
RA Li W., Guan K.L.;
RT "The Down syndrome cell adhesion molecule (DSCAM) interacts with and
RT activates Pak.";
RL J. Biol. Chem. 279:32824-32831(2004).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic brain;
RX PubMed=15345747; DOI=10.1074/mcp.m400085-mcp200;
RA Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.;
RT "Phosphoproteomic analysis of the developing mouse brain.";
RL Mol. Cell. Proteomics 3:1093-1101(2004).
RN [9]
RP FUNCTION, AND MUTAGENESIS OF HIS-83; HIS-86; LYS-299 AND THR-423.
RX PubMed=15800193; DOI=10.1523/jneurosci.3553-04.2005;
RA Zhang H., Webb D.J., Asmussen H., Niu S., Horwitz A.F.;
RT "A GIT1/PIX/Rac/PAK signaling module regulates spine morphogenesis and
RT synapse formation through MLC.";
RL J. Neurosci. 25:3379-3388(2005).
RN [10]
RP INTERACTION WITH SCRIB.
RX PubMed=18716323; DOI=10.1093/hmg/ddn248;
RA Nola S., Sebbagh M., Marchetto S., Osmani N., Nourry C., Audebert S.,
RA Navarro C., Rachel R., Montcouquiol M., Sans N., Etienne-Manneville S.,
RA Borg J.-P., Santoni M.-J.;
RT "Scrib regulates PAK activity during the cell migration process.";
RL Hum. Mol. Genet. 17:3552-3565(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-212; SER-220; SER-223;
RP THR-225; THR-229 AND THR-230, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [12]
RP FUNCTION, INTERACTION WITH BRSK2, AND PHOSPHORYLATION AT THR-423.
RX PubMed=22669945; DOI=10.1074/jbc.m112.378372;
RA Nie J., Sun C., Faruque O., Ye G., Li J., Liang Q., Chang Z., Yang W.,
RA Han X., Shi Y.;
RT "Synapses of amphids defective (SAD-A) kinase promotes glucose-stimulated
RT insulin secretion through activation of p21-activated kinase (PAK1) in
RT pancreatic beta-Cells.";
RL J. Biol. Chem. 287:26435-26444(2012).
RN [13]
RP PHOSPHORYLATION.
RX PubMed=22685302; DOI=10.1074/jbc.m112.340174;
RA Purohit A.A., Li W., Qu C., Dwyer T., Shao Q., Guan K.L., Liu G.;
RT "Down syndrome cell adhesion molecule (DSCAM) associates with
RT uncoordinated-5C (UNC5C) in netrin-1-mediated growth cone collapse.";
RL J. Biol. Chem. 287:27126-27138(2012).
RN [14]
RP INTERACTION WITH INPP5K.
RX PubMed=22751929; DOI=10.1128/mcb.00636-12;
RA Ijuin T., Takenawa T.;
RT "Regulation of insulin signaling by the phosphatidylinositol 3,4,5-
RT triphosphate phosphatase SKIP through the scaffolding function of Pak1.";
RL Mol. Cell. Biol. 32:3570-3584(2012).
RN [15]
RP FUNCTION, AND PHOSPHORYLATION.
RX PubMed=23633677; DOI=10.1126/scisignal.2003627;
RA Borroni E.M., Cancellieri C., Vacchini A., Benureau Y., Lagane B.,
RA Bachelerie F., Arenzana-Seisdedos F., Mizuno K., Mantovani A., Bonecchi R.,
RA Locati M.;
RT "Beta-arrestin-dependent activation of the cofilin pathway is required for
RT the scavenging activity of the atypical chemokine receptor D6.";
RL Sci. Signal. 6:RA30-RA30(2013).
CC -!- FUNCTION: Protein kinase involved in intracellular signaling pathways
CC downstream of integrins and receptor-type kinases that plays an
CC important role in cytoskeleton dynamics, in cell adhesion, migration,
CC proliferation, apoptosis, mitosis, and in vesicle-mediated transport
CC processes. Can directly phosphorylate BAD and protects cells against
CC apoptosis. Activated by interaction with CDC42 and RAC1. Functions as
CC GTPase effector that links the Rho-related GTPases CDC42 and RAC1 to
CC the JNK MAP kinase pathway. Phosphorylates and activates MAP2K1, and
CC thereby mediates activation of downstream MAP kinases. Involved in the
CC reorganization of the actin cytoskeleton, actin stress fibers and of
CC focal adhesion complexes. Phosphorylates the tubulin chaperone TBCB and
CC thereby plays a role in the regulation of microtubule biogenesis and
CC organization of the tubulin cytoskeleton. Plays a role in the
CC regulation of insulin secretion in response to elevated glucose levels.
CC Part of a ternary complex that contains PAK1, DVL1 and MUSK that is
CC important for MUSK-dependent regulation of AChR clustering during the
CC formation of the neuromuscular junction (NMJ). Activity is inhibited in
CC cells undergoing apoptosis, potentially due to binding of CDC2L1 and
CC CDC2L2. Phosphorylates MYL9/MLC2. Phosphorylates RAF1 at 'Ser-338' and
CC 'Ser-339' resulting in: activation of RAF1, stimulation of RAF1
CC translocation to mitochondria, phosphorylation of BAD by RAF1, and RAF1
CC binding to BCL2. Phosphorylates SNAI1 at 'Ser-246' promoting its
CC transcriptional repressor activity by increasing its accumulation in
CC the nucleus. In podocytes, promotes NR3C2 nuclear localization.
CC Required for atypical chemokine receptor ACKR2-induced phosphorylation
CC of LIMK1 and cofilin (CFL1) and for the up-regulation of ACKR2 from
CC endosomal compartment to cell membrane, increasing its efficiency in
CC chemokine uptake and degradation. In synapses, seems to mediate the
CC regulation of F-actin cluster formation performed by SHANK3, maybe
CC through CFL1 phosphorylation and inactivation. Plays a role in RUFY3-
CC mediated facilitating gastric cancer cells migration and invasion. In
CC response to DNA damage, phosphorylates MORC2 which activates its ATPase
CC activity and facilitates chromatin remodeling (By similarity). In
CC neurons, plays a crucial role in regulating GABA(A) receptor synaptic
CC stability and hence GABAergic inhibitory synaptic transmission through
CC its role in F-actin stabilization (By similarity). In hippocampal
CC neurons, necessary for the formation of dendritic spines and excitatory
CC synapses; this function is dependent on kinase activity and may be
CC exerted by the regulation of actomyosin contractility through the
CC phosphorylation of myosin II regulatory light chain (MLC)
CC (PubMed:15800193). Along with GIT1, positively regulates microtubule
CC nucleation during interphase (By similarity).
CC {ECO:0000250|UniProtKB:P35465, ECO:0000250|UniProtKB:Q13153,
CC ECO:0000269|PubMed:10611223, ECO:0000269|PubMed:12165471,
CC ECO:0000269|PubMed:12176334, ECO:0000269|PubMed:15800193,
CC ECO:0000269|PubMed:22669945, ECO:0000269|PubMed:23633677}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000250|UniProtKB:Q13153};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000250|UniProtKB:Q13153};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC -!- ACTIVITY REGULATION: Phosphorylation of Thr-84 by OXSR1 inhibits
CC activation (By similarity). Activated by binding small G proteins.
CC Binding of GTP-bound CDC42 or RAC1 to the autoregulatory region
CC releases monomers from the autoinhibited dimer, and enables activation
CC by phosphorylation of Thr-423 (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homodimer in its autoinhibited state. Active as monomer.
CC Interacts with GIT1 (By similarity). Component of cytoplasmic
CC complexes, which also contains PXN, ARHGEF7 and GIT1. Interacts with
CC NISCH (PubMed:15229651). Interacts with DVL1; mediates the formation of
CC a DVL1, MUSK and PAK1 ternary complex involved in AChR clustering (By
CC similarity). Binds to the caspase-cleaved p110 isoform of CDC2L1 and
CC CDC2L2, p110C, but not the full-length proteins (By similarity).
CC Interacts with ARHGEF7 (By similarity). Interacts tightly with GTP-
CC bound but not GDP-bound CDC42/P21 and RAC1. Probably found in a ternary
CC complex composed of DSCAM, PAK1 and RAC1. Interacts with DSCAM (via
CC cytoplasmic domain); the interaction is direct and enhanced in presence
CC of RAC1 (PubMed:15169762). Interacts with SCRIB (PubMed:18716323).
CC Interacts with PDPK1 (By similarity). Interacts (via kinase domain)
CC with RAF1 (By similarity). Interacts with NCK1 and NCK2 (By
CC similarity). Interacts with TBCB (By similarity). Interacts with BRSK2
CC (PubMed:22669945). Interacts with SNAI1 (By similarity). Interacts with
CC CIB1 (via N-terminal region); the interaction is direct, promotes PAK1
CC activity and occurs in a calcium-dependent manner (By similarity).
CC Interacts with INPP5K (PubMed:22751929). Interacts with gamma-tubulin
CC (By similarity). {ECO:0000250|UniProtKB:P35465,
CC ECO:0000250|UniProtKB:Q13153, ECO:0000269|PubMed:15169762,
CC ECO:0000269|PubMed:15229651, ECO:0000269|PubMed:18716323,
CC ECO:0000269|PubMed:22751929}.
CC -!- INTERACTION:
CC O88643; P60766: Cdc42; NbExp=2; IntAct=EBI-457240, EBI-81763;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q13153}. Cell
CC junction, focal adhesion {ECO:0000250|UniProtKB:Q13153}. Cell
CC projection, lamellipodium {ECO:0000250|UniProtKB:Q13153}. Cell membrane
CC {ECO:0000250|UniProtKB:Q13153}. Cell projection, ruffle membrane
CC {ECO:0000250|UniProtKB:Q13153}. Cell projection, invadopodium
CC {ECO:0000250|UniProtKB:Q13153}. Nucleus, nucleoplasm
CC {ECO:0000250|UniProtKB:Q13153}. Chromosome
CC {ECO:0000250|UniProtKB:Q13153}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000250|UniProtKB:Q13153}.
CC Note=Recruited to the cell membrane by interaction with CDC42 and RAC1
CC (By similarity). Recruited to focal adhesions upon activation.
CC Colocalized with CIB1 within membrane ruffles during cell spreading
CC upon readhesion to fibronectin. Colocalizes with RUFY3, F-actin and
CC other core migration components in invadopodia at the cell periphery
CC (By similarity). Upon DNA damage, translocates to the nucleoplasm when
CC phosphorylated at Thr-212 where is co-recruited with MORC2 on damaged
CC chromatin (By similarity). Localization to the centrosome does not
CC depend upon the presence of gamma-tubulin (By similarity). Localization
CC of the active, but not inactive, protein to the adhesions and edge of
CC lamellipodia is mediated by interaction with GIT1 (By similarity).
CC {ECO:0000250|UniProtKB:P35465, ECO:0000250|UniProtKB:Q13153}.
CC -!- PTM: Autophosphorylated in trans, meaning that in a dimer, one kinase
CC molecule phosphorylates the other one. Activated by autophosphorylation
CC at Thr-423 in response to a conformation change, triggered by
CC interaction with GTP-bound CDC42 or RAC1. Activated by phosphorylation
CC at Thr-423 by BRSK2 and by PDPK1. Phosphorylated by JAK2 in response to
CC PRL; this increases PAK1 kinase activity. Phosphorylated at Ser-21 by
CC PKB/AKT; this reduces interaction with NCK1 and association with focal
CC adhesion sites (By similarity). Upon DNA damage, phosphorylated at Thr-
CC 212 and translocates to the nucleoplasm (By similarity). Phosphorylated
CC at tyrosine residues, which can be enhanced by NTN1 (PubMed:22685302).
CC {ECO:0000250|UniProtKB:P35465, ECO:0000250|UniProtKB:Q13153,
CC ECO:0000269|PubMed:22685302}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. STE20 subfamily. {ECO:0000305}.
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DR EMBL; AF082077; AAC32375.1; -; mRNA.
DR AlphaFoldDB; O88643; -.
DR BMRB; O88643; -.
DR SMR; O88643; -.
DR DIP; DIP-32847N; -.
DR IntAct; O88643; 16.
DR MINT; O88643; -.
DR STRING; 10090.ENSMUSP00000033040; -.
DR BindingDB; O88643; -.
DR ChEMBL; CHEMBL4295682; -.
DR iPTMnet; O88643; -.
DR PhosphoSitePlus; O88643; -.
DR jPOST; O88643; -.
DR MaxQB; O88643; -.
DR PaxDb; O88643; -.
DR PeptideAtlas; O88643; -.
DR PRIDE; O88643; -.
DR ProteomicsDB; 293997; -.
DR MGI; MGI:1339975; Pak1.
DR eggNOG; KOG0578; Eukaryota.
DR InParanoid; O88643; -.
DR PhylomeDB; O88643; -.
DR BRENDA; 2.7.11.1; 3474.
DR Reactome; R-MMU-202433; Generation of second messenger molecules.
DR Reactome; R-MMU-2029482; Regulation of actin dynamics for phagocytic cup formation.
DR Reactome; R-MMU-2871796; FCERI mediated MAPK activation.
DR Reactome; R-MMU-376172; DSCAM interactions.
DR Reactome; R-MMU-389359; CD28 dependent Vav1 pathway.
DR Reactome; R-MMU-3928662; EPHB-mediated forward signaling.
DR Reactome; R-MMU-3928664; Ephrin signaling.
DR Reactome; R-MMU-399954; Sema3A PAK dependent Axon repulsion.
DR Reactome; R-MMU-445144; Signal transduction by L1.
DR Reactome; R-MMU-445355; Smooth Muscle Contraction.
DR Reactome; R-MMU-5218920; VEGFR2 mediated vascular permeability.
DR Reactome; R-MMU-5621575; CD209 (DC-SIGN) signaling.
DR Reactome; R-MMU-5627123; RHO GTPases activate PAKs.
DR Reactome; R-MMU-5687128; MAPK6/MAPK4 signaling.
DR Reactome; R-MMU-8964616; G beta:gamma signalling through CDC42.
DR Reactome; R-MMU-9013148; CDC42 GTPase cycle.
DR Reactome; R-MMU-9013149; RAC1 GTPase cycle.
DR Reactome; R-MMU-9013404; RAC2 GTPase cycle.
DR Reactome; R-MMU-9013406; RHOQ GTPase cycle.
DR Reactome; R-MMU-9013407; RHOH GTPase cycle.
DR Reactome; R-MMU-9013409; RHOJ GTPase cycle.
DR Reactome; R-MMU-9013420; RHOU GTPase cycle.
DR Reactome; R-MMU-9013423; RAC3 GTPase cycle.
DR Reactome; R-MMU-9013424; RHOV GTPase cycle.
DR ChiTaRS; Pak1; mouse.
DR PRO; PR:O88643; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; O88643; protein.
DR GO; GO:0005884; C:actin filament; ISO:MGI.
DR GO; GO:0030424; C:axon; IDA:MGI.
DR GO; GO:0005911; C:cell-cell junction; ISS:UniProtKB.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0030425; C:dendrite; IDA:MGI.
DR GO; GO:0005925; C:focal adhesion; TAS:MGI.
DR GO; GO:0098982; C:GABA-ergic synapse; IDA:SynGO.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0030426; C:growth cone; IDA:MGI.
DR GO; GO:0014704; C:intercalated disc; ISO:MGI.
DR GO; GO:0030027; C:lamellipodium; ISO:MGI.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell.
DR GO; GO:0031965; C:nuclear membrane; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0014069; C:postsynaptic density; IDA:MGI.
DR GO; GO:0098793; C:presynapse; IEA:GOC.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0001726; C:ruffle; ISS:UniProtKB.
DR GO; GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030018; C:Z disc; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005518; F:collagen binding; ISS:UniProtKB.
DR GO; GO:0043015; F:gamma-tubulin binding; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0004672; F:protein kinase activity; IDA:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:MGI.
DR GO; GO:0031267; F:small GTPase binding; ISO:MGI.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; ISS:UniProtKB.
DR GO; GO:0021764; P:amygdala development; IGI:MGI.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0048754; P:branching morphogenesis of an epithelial tube; ISS:UniProtKB.
DR GO; GO:0016477; P:cell migration; ISO:MGI.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0032869; P:cellular response to insulin stimulus; ISO:MGI.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IDA:MGI.
DR GO; GO:0006338; P:chromatin remodeling; ISS:UniProtKB.
DR GO; GO:0016358; P:dendrite development; IDA:MGI.
DR GO; GO:0060996; P:dendritic spine development; IGI:MGI.
DR GO; GO:0030010; P:establishment of cell polarity; ISO:MGI.
DR GO; GO:0006887; P:exocytosis; IEA:UniProtKB-KW.
DR GO; GO:0061534; P:gamma-aminobutyric acid secretion, neurotransmission; IGI:MGI.
DR GO; GO:0061535; P:glutamate secretion, neurotransmission; IGI:MGI.
DR GO; GO:0048012; P:hepatocyte growth factor receptor signaling pathway; ISO:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0061052; P:negative regulation of cell growth involved in cardiac muscle cell development; ISO:MGI.
DR GO; GO:0060244; P:negative regulation of cell proliferation involved in contact inhibition; ISS:UniProtKB.
DR GO; GO:0007528; P:neuromuscular junction development; IGI:MGI.
DR GO; GO:0048812; P:neuron projection morphogenesis; ISO:MGI.
DR GO; GO:0098597; P:observational learning; IGI:MGI.
DR GO; GO:0016310; P:phosphorylation; ISO:MGI.
DR GO; GO:0045773; P:positive regulation of axon extension; ISO:MGI.
DR GO; GO:0030335; P:positive regulation of cell migration; ISS:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0010763; P:positive regulation of fibroblast migration; ISO:MGI.
DR GO; GO:0046628; P:positive regulation of insulin receptor signaling pathway; ISO:MGI.
DR GO; GO:0033148; P:positive regulation of intracellular estrogen receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0043507; P:positive regulation of JUN kinase activity; ISS:UniProtKB.
DR GO; GO:0090063; P:positive regulation of microtubule nucleation; ISS:UniProtKB.
DR GO; GO:0031116; P:positive regulation of microtubule polymerization; ISO:MGI.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; ISS:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0090314; P:positive regulation of protein targeting to membrane; ISO:MGI.
DR GO; GO:0051496; P:positive regulation of stress fiber assembly; ISS:UniProtKB.
DR GO; GO:1904754; P:positive regulation of vascular associated smooth muscle cell migration; ISO:MGI.
DR GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; ISO:MGI.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0043113; P:receptor clustering; IGI:MGI.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; ISO:MGI.
DR GO; GO:0050770; P:regulation of axonogenesis; IBA:GO_Central.
DR GO; GO:0010468; P:regulation of gene expression; IGI:MGI.
DR GO; GO:1900271; P:regulation of long-term synaptic potentiation; IGI:MGI.
DR GO; GO:0043408; P:regulation of MAPK cascade; IGI:MGI.
DR GO; GO:0001666; P:response to hypoxia; ISO:MGI.
DR GO; GO:0010033; P:response to organic substance; ISO:MGI.
DR GO; GO:0099553; P:trans-synaptic signaling by endocannabinoid, modulating synaptic transmission; IDA:SynGO.
DR GO; GO:0019226; P:transmission of nerve impulse; IGI:MGI.
DR GO; GO:0042060; P:wound healing; ISS:UniProtKB.
DR CDD; cd01093; CRIB_PAK_like; 1.
DR Gene3D; 3.90.810.10; -; 1.
DR InterPro; IPR000095; CRIB_dom.
DR InterPro; IPR036936; CRIB_dom_sf.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR033923; PAK_BD.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00786; PBD; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00285; PBD; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50108; CRIB; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW Acetylation; Allosteric enzyme; Apoptosis; ATP-binding; Cell junction;
KW Cell membrane; Cell projection; Chromosome; Cytoplasm; Cytoskeleton;
KW Direct protein sequencing; Exocytosis; Kinase; Membrane;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q13153"
FT CHAIN 2..545
FT /note="Serine/threonine-protein kinase PAK 1"
FT /id="PRO_0000086461"
FT DOMAIN 75..88
FT /note="CRIB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00057"
FT DOMAIN 270..521
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..75
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 70..140
FT /note="Autoregulatory region"
FT /evidence="ECO:0000250"
FT REGION 70..105
FT /note="GTPase-binding"
FT /evidence="ECO:0000250"
FT REGION 150..198
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 210..250
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 21..38
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 42..75
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 150..167
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 216..236
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 389
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 276..284
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 299
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:Q13153"
FT MOD_RES 21
FT /note="Phosphoserine; by PKB and autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q13153"
FT MOD_RES 57
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q13153"
FT MOD_RES 84
FT /note="Phosphothreonine; by OXSR1"
FT /evidence="ECO:0000250|UniProtKB:P35465"
FT MOD_RES 115
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13153"
FT MOD_RES 131
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q13153"
FT MOD_RES 142
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q13153"
FT MOD_RES 144
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P35465"
FT MOD_RES 149
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P35465"
FT MOD_RES 153
FT /note="Phosphotyrosine; by JAK2"
FT /evidence="ECO:0000250|UniProtKB:Q13153"
FT MOD_RES 174
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13153"
FT MOD_RES 185
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q13153"
FT MOD_RES 199
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P35465"
FT MOD_RES 201
FT /note="Phosphotyrosine; by JAK2"
FT /evidence="ECO:0000250|UniProtKB:Q13153"
FT MOD_RES 204
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P35465"
FT MOD_RES 212
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:12176334,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 219
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q13153"
FT MOD_RES 220
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 223
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 225
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 229
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 230
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 285
FT /note="Phosphotyrosine; by JAK2"
FT /evidence="ECO:0000250|UniProtKB:Q13153"
FT MOD_RES 423
FT /note="Phosphothreonine; by autocatalysis, BRSK2 and PDPK1"
FT /evidence="ECO:0000269|PubMed:22669945"
FT MUTAGEN 83
FT /note="H->L: When expressed in hippocampal neurons,
FT strongly decreases the number of dendritic spines; when
FT associated with L-86 and R-299."
FT /evidence="ECO:0000269|PubMed:15800193"
FT MUTAGEN 86
FT /note="H->L: When expressed in hippocampal neurons,
FT strongly decreases the number of dendritic spines; when
FT associated with L-83 and R-299."
FT /evidence="ECO:0000269|PubMed:15800193"
FT MUTAGEN 299
FT /note="K->R: When expressed in hippocampal neurons,
FT decreases the number of dendritic spines. Strong decrease
FT in the number of dendritic spines; when associated with L-
FT 83 and L-86."
FT /evidence="ECO:0000269|PubMed:15800193"
FT MUTAGEN 423
FT /note="T->E: When expressed in hippocampal neurons,
FT increases the density of both spines and dendritic
FT protrusions."
FT /evidence="ECO:0000269|PubMed:15800193"
SQ SEQUENCE 545 AA; 60737 MW; A4861289534C3819 CRC64;
MSNNGVDIQD KPPAPPMRNT STMIGAGSKD TGTLNHGSKP LPPNPEEKKK KDRFYRSILP
GDKTNKKREK ERPEISLPSD FEHTIHVGFD AVTGEFTGMP EQWARLLQTS NITKSEQKKN
PQAVLDVLEF YNSKKTSNSK KYMSFTDKSA EDYNSSNTLN VKTVSETPAV PPVSEDDEDD
DDDATPPPVI APRPEHTKSV YTRSVIEPLP VTPTRDVATS PISPTENNTT PPDALTRNTE
KQKKKPKMSD EEILEKLRSI VSVGDPKKKY TPFEKIGQGA SGTVYTAMDV ATGQEVAIKQ
MNLQQQPKKE LIINEILVMR ENKNPNIVNY LDSYLVGDEL WVVMEYLAGG SLTDVVTETC
MDEGQIAAVC RECLQALEFL HSNQVIHRDI KSDNILLGMD GSVKLTDFGF CAQITPEQSK
RSTMVGTPYW MAPEVVTRKA YGPKVDIWSL GIMAIEMIEG EPPYLNENPL RALYLIATNG
TPELQNPEKL SAIFRDFLQC CLEMDVEKRG SAKELLQHQF LKIAKPLSSL TPLMHAAKEA
TKNNH
