PAK1_RAT
ID PAK1_RAT Reviewed; 544 AA.
AC P35465; Q62934;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-1998, sequence version 3.
DT 03-AUG-2022, entry version 214.
DE RecName: Full=Serine/threonine-protein kinase PAK 1 {ECO:0000305};
DE EC=2.7.11.1 {ECO:0000269|PubMed:9032240};
DE AltName: Full=Alpha-PAK {ECO:0000250|UniProtKB:Q13153};
DE AltName: Full=Protein kinase MUK2 {ECO:0000303|Ref.3};
DE AltName: Full=p21-activated kinase 1 {ECO:0000250|UniProtKB:Q13153};
DE Short=PAK-1;
DE AltName: Full=p68-PAK {ECO:0000303|PubMed:8107774};
GN Name=Pak1 {ECO:0000312|RGD:3250};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=8107774; DOI=10.1038/367040a0;
RA Manser E., Leung T., Salihuddin H., Zhao Z.-S., Lim L.;
RT "A brain serine/threonine protein kinase activated by Cdc42 and Rac1.";
RL Nature 367:40-46(1994).
RN [2]
RP SEQUENCE REVISION.
RA Zhao Z.-S.;
RL Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Osada S., Izawa M., Saito R., Mizuno K., Suzuki A., Hirai S., Ohno S.;
RL Submitted (JUL-1996) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP TISSUE SPECIFICITY.
RX PubMed=7559638; DOI=10.1074/jbc.270.42.25070;
RA Manser E., Chong C., Zhao Z.-S., Leung T., Michael G., Hall C., Lim L.;
RT "Molecular cloning of a new member of the p21-Cdc42/Rac-activated kinase
RT (PAK) family.";
RL J. Biol. Chem. 270:25070-25078(1995).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, INTERACTION WITH CDC42
RP AND RAC1, ACTIVITY REGULATION, SUBCELLULAR LOCATION, MUTAGENESIS OF LEU-404
RP AND THR-422, PARTIAL PROTEIN SEQUENCE, AND PHOSPHORYLATION AT SER-21;
RP SER-57; SER-144; SER-149; SER-198; SER-203 AND THR-422.
RX PubMed=9032240; DOI=10.1128/mcb.17.3.1129;
RA Manser E., Huang H.Y., Loo T.H., Chen X.Q., Dong J.M., Leung T., Lim L.;
RT "Expression of constitutively active alpha-PAK reveals effects of the
RT kinase on actin and focal complexes.";
RL Mol. Cell. Biol. 17:1129-1143(1997).
RN [6]
RP DOMAIN GTPASE BINDING.
RX PubMed=9601050; DOI=10.1021/bi980140+;
RA Thompson G., Owen D., Chalk P.A., Lowe P.N.;
RT "Delineation of the Cdc42/Rac-binding domain of p21-activated kinase.";
RL Biochemistry 37:7885-7891(1998).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, ACTIVITY REGULATION, AUTOREGULATORY REGION,
RP AND MUTAGENESIS OF HIS-83; HIS-86 AND LEU-107.
RX PubMed=9774440; DOI=10.1074/jbc.273.43.28191;
RA Frost J.A., Khokhlatchev A., Stippec S., White M.A., Cobb M.H.;
RT "Differential effects of PAK1-activating mutations reveal activity-
RT dependent and -independent effects on cytoskeletal regulation.";
RL J. Biol. Chem. 273:28191-28198(1998).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND AUTOREGULATORY DOMAIN.
RX PubMed=9528787; DOI=10.1128/mcb.18.4.2153;
RA Zhao Z.S., Manser E., Chen X.Q., Chong C., Leung T., Lim L.;
RT "A conserved negative regulatory region in alphaPAK: inhibition of PAK
RT kinases reveals their morphological roles downstream of Cdc42 and Rac1.";
RL Mol. Cell. Biol. 18:2153-2163(1998).
RN [9]
RP MUTAGENESIS OF SER-144; SER-149 AND THR-422.
RX PubMed=11278486; DOI=10.1074/jbc.m009316200;
RA Chong C., Tan L., Lim L., Manser E.;
RT "The mechanism of PAK activation. Autophosphorylation events in both
RT regulatory and kinase domains control activity.";
RL J. Biol. Chem. 276:17347-17353(2001).
RN [10]
RP FUNCTION.
RX PubMed=12876277; DOI=10.1083/jcb.200212141;
RA Slack-Davis J.K., Eblen S.T., Zecevic M., Boerner S.A., Tarcsafalvi A.,
RA Diaz H.B., Marshall M.S., Weber M.J., Parsons J.T., Catling A.D.;
RT "PAK1 phosphorylation of MEK1 regulates fibronectin-stimulated MAPK
RT activation.";
RL J. Cell Biol. 162:281-291(2003).
RN [11]
RP FUNCTION, ACTIVITY REGULATION, INTERACTION WITH OXSR1, PHOSPHORYLATION AT
RP THR-84, AND MUTAGENESIS OF THR-84.
RX PubMed=14707132; DOI=10.1074/jbc.m313562200;
RA Chen W., Yazicioglu M., Cobb M.H.;
RT "Characterization of OSR1, a member of the mammalian Ste20p/germinal center
RT kinase subfamily.";
RL J. Biol. Chem. 279:11129-11136(2004).
RN [12]
RP FUNCTION.
RX PubMed=19029984; DOI=10.1038/nm.1879;
RA Shibata S., Nagase M., Yoshida S., Kawarazaki W., Kurihara H., Tanaka H.,
RA Miyoshi J., Takai Y., Fujita T.;
RT "Modification of mineralocorticoid receptor function by Rac1 GTPase:
RT implication in proteinuric kidney disease.";
RL Nat. Med. 14:1370-1376(2008).
RN [13]
RP PHOSPHORYLATION AT THR-422.
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 [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-174 AND SER-222, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [15]
RP FUNCTION IN ACTIN POLYMERIZATION, PHOSPHORYLATION AT THR-422, AND
RP MUTAGENESIS OF HIS-83; HIS-86; LYS-298 AND THR-422.
RX PubMed=24089484; DOI=10.1523/jneurosci.1175-13.2013;
RA Duffney L.J., Wei J., Cheng J., Liu W., Smith K.R., Kittler J.T., Yan Z.;
RT "Shank3 deficiency induces NMDA receptor hypofunction via an actin-
RT dependent mechanism.";
RL J. Neurosci. 33:15767-15778(2013).
RN [16]
RP FUNCTION.
RX PubMed=25284783; DOI=10.1016/j.celrep.2014.08.061;
RA Smith K.R., Davenport E.C., Wei J., Li X., Pathania M., Vaccaro V., Yan Z.,
RA Kittler J.T.;
RT "GIT1 and betaPIX are essential for GABA(A) receptor synaptic stability and
RT inhibitory neurotransmission.";
RL Cell Rep. 9:298-310(2014).
RN [17]
RP STRUCTURE BY NMR OF 75-118 IN COMPLEX WITH CDC42, AND INTERACTION WITH
RP CDC42.
RX PubMed=10802735; DOI=10.1038/75158;
RA Morreale A., Venkatesan M., Mott H.R., Owen D., Nietlispach D., Lowe P.N.,
RA Laue E.D.;
RT "Structure of Cdc42 bound to the GTPase binding domain of PAK.";
RL Nat. Struct. Biol. 7:384-388(2000).
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 (PubMed:25284783). 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) (By
CC similarity). Along with GIT1, positively regulates microtubule
CC nucleation during interphase (By similarity).
CC {ECO:0000250|UniProtKB:O88643, ECO:0000250|UniProtKB:Q13153,
CC ECO:0000269|PubMed:12876277, ECO:0000269|PubMed:14707132,
CC ECO:0000269|PubMed:19029984, ECO:0000269|PubMed:24089484,
CC ECO:0000269|PubMed:25284783, ECO:0000269|PubMed:9032240,
CC ECO:0000269|PubMed:9528787, ECO:0000269|PubMed:9774440}.
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:0000269|PubMed:9032240};
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:0000269|PubMed:9032240};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
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-422. {ECO:0000250|UniProtKB:Q13153,
CC ECO:0000269|PubMed:14707132, ECO:0000269|PubMed:9032240,
CC ECO:0000269|PubMed:9774440}.
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 (By similarity). Interacts with DVL1; mediates the formation of a
CC 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). Probably found in a ternary
CC complex composed of DSCAM, PAK1 and RAC1 (By similarity). Interacts
CC with DSCAM (via cytoplasmic domain); the interaction is direct and
CC enhanced in presence of RAC1. Interacts with SCRIB (By similarity).
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 (By similarity). Interacts tightly with GTP-bound but not GDP-bound
CC CDC42/P21 and RAC1 (PubMed:9032240). Interacts with SNAI1 (By
CC similarity). Interacts with CIB1 (via N-terminal region); the
CC interaction is direct, promotes PAK1 activity and occurs in a calcium-
CC dependent manner. Interacts with INPP5K (By similarity). Interacts with
CC gamma-tubulin (By similarity). {ECO:0000250|UniProtKB:O88643,
CC ECO:0000250|UniProtKB:Q13153, ECO:0000269|PubMed:9032240}.
CC -!- INTERACTION:
CC P35465; P20152: Vim; Xeno; NbExp=2; IntAct=EBI-444379, EBI-299269;
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, ECO:0000269|PubMed:9032240}. Cell
CC projection, ruffle membrane {ECO:0000250|UniProtKB:Q13153}. Cell
CC projection, invadopodium {ECO:0000250|UniProtKB:Q13153}. Nucleus,
CC nucleoplasm {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 Recruited to focal adhesions upon activation. Colocalized with CIB1
CC within membrane ruffles during cell spreading upon readhesion to
CC fibronectin. Colocalizes with RUFY3, F-actin and other core migration
CC components in invadopodia at the cell periphery (By similarity). Upon
CC DNA damage, translocates to the nucleoplasm when phosphorylated at Thr-
CC 212 where is co-recruited with MORC2 on damaged chromatin (By
CC similarity). Localization to the centrosome does not depend upon the
CC presence of gamma-tubulin (By similarity). Localization of the active,
CC but not inactive, protein to the adhesions and edge of lamellipodia is
CC mediated by interaction with GIT1 (By similarity).
CC {ECO:0000250|UniProtKB:Q13153}.
CC -!- TISSUE SPECIFICITY: Expressed predominantly in the brain, with higher
CC expression in neuronal groups associated with motor function, and at
CC lower levels in the spleen. {ECO:0000269|PubMed:7559638}.
CC -!- DEVELOPMENTAL STAGE: Found in the embryonic CNS with little expression
CC elsewhere.
CC -!- PTM: Autophosphorylated in trans, meaning that in a dimer, one kinase
CC molecule phosphorylates the other one. Activated by autophosphorylation
CC at Thr-422 in response to a conformation change, triggered by
CC interaction with GTP-bound CDC42 or RAC1. Activated by phosphorylation
CC at Thr-422 by PDPK1. Phosphorylated by JAK2 in response to PRL; this
CC increases PAK1 kinase activity. Phosphorylated at Ser-21 by PKB/AKT;
CC this reduces interaction with NCK1 and association with focal adhesion
CC sites (By similarity). Activated by phosphorylation at Thr-422 by
CC BRSK2. Upon DNA damage, phosphorylated at Thr-211 and translocates to
CC the nucleoplasm (By similarity). Phosphorylated at tyrosine residues,
CC which can be enhanced by NTN1 (By similarity).
CC {ECO:0000250|UniProtKB:O88643, ECO:0000250|UniProtKB:Q13153,
CC ECO:0000269|PubMed:14707132, ECO:0000269|PubMed:22669945,
CC ECO:0000269|PubMed:24089484, ECO:0000269|PubMed:9032240}.
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; U23443; AAB95646.1; -; mRNA.
DR EMBL; U49953; AAB61533.1; -; mRNA.
DR PIR; S40482; S40482.
DR RefSeq; NP_058894.1; NM_017198.1.
DR RefSeq; XP_006229814.1; XM_006229752.2.
DR RefSeq; XP_006229815.1; XM_006229753.2.
DR RefSeq; XP_006229816.1; XM_006229754.3.
DR PDB; 1E0A; NMR; -; B=75-118.
DR PDBsum; 1E0A; -.
DR AlphaFoldDB; P35465; -.
DR BMRB; P35465; -.
DR SMR; P35465; -.
DR BioGRID; 248078; 1.
DR DIP; DIP-32990N; -.
DR ELM; P35465; -.
DR IntAct; P35465; 6.
DR MINT; P35465; -.
DR STRING; 10116.ENSRNOP00000045832; -.
DR ChEMBL; CHEMBL3580528; -.
DR iPTMnet; P35465; -.
DR PhosphoSitePlus; P35465; -.
DR SwissPalm; P35465; -.
DR jPOST; P35465; -.
DR PaxDb; P35465; -.
DR PRIDE; P35465; -.
DR Ensembl; ENSRNOT00000091952; ENSRNOP00000073036; ENSRNOG00000029784.
DR GeneID; 29431; -.
DR KEGG; rno:29431; -.
DR CTD; 5058; -.
DR RGD; 3250; Pak1.
DR eggNOG; KOG0578; Eukaryota.
DR GeneTree; ENSGT00950000182988; -.
DR HOGENOM; CLU_000288_26_6_1; -.
DR InParanoid; P35465; -.
DR OMA; IEISTPY; -.
DR OrthoDB; 757766at2759; -.
DR PhylomeDB; P35465; -.
DR TreeFam; TF105351; -.
DR BRENDA; 2.7.11.1; 5301.
DR Reactome; R-RNO-202433; Generation of second messenger molecules.
DR Reactome; R-RNO-2029482; Regulation of actin dynamics for phagocytic cup formation.
DR Reactome; R-RNO-2871796; FCERI mediated MAPK activation.
DR Reactome; R-RNO-376172; DSCAM interactions.
DR Reactome; R-RNO-389359; CD28 dependent Vav1 pathway.
DR Reactome; R-RNO-3928662; EPHB-mediated forward signaling.
DR Reactome; R-RNO-3928664; Ephrin signaling.
DR Reactome; R-RNO-399954; Sema3A PAK dependent Axon repulsion.
DR Reactome; R-RNO-445144; Signal transduction by L1.
DR Reactome; R-RNO-445355; Smooth Muscle Contraction.
DR Reactome; R-RNO-5218920; VEGFR2 mediated vascular permeability.
DR Reactome; R-RNO-5621575; CD209 (DC-SIGN) signaling.
DR Reactome; R-RNO-5627123; RHO GTPases activate PAKs.
DR Reactome; R-RNO-5687128; MAPK6/MAPK4 signaling.
DR Reactome; R-RNO-8964616; G beta:gamma signalling through CDC42.
DR Reactome; R-RNO-9013148; CDC42 GTPase cycle.
DR Reactome; R-RNO-9013149; RAC1 GTPase cycle.
DR Reactome; R-RNO-9013404; RAC2 GTPase cycle.
DR Reactome; R-RNO-9013406; RHOQ GTPase cycle.
DR Reactome; R-RNO-9013407; RHOH GTPase cycle.
DR Reactome; R-RNO-9013409; RHOJ GTPase cycle.
DR Reactome; R-RNO-9013420; RHOU GTPase cycle.
DR Reactome; R-RNO-9013423; RAC3 GTPase cycle.
DR Reactome; R-RNO-9013424; RHOV GTPase cycle.
DR EvolutionaryTrace; P35465; -.
DR PRO; PR:P35465; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000029784; Expressed in cerebellum and 19 other tissues.
DR Genevisible; P35465; RN.
DR GO; GO:0005884; C:actin filament; ISO:RGD.
DR GO; GO:0030424; C:axon; IDA:RGD.
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; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0005925; C:focal adhesion; IEA:UniProtKB-SubCell.
DR GO; GO:0098982; C:GABA-ergic synapse; ISO:RGD.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:RGD.
DR GO; GO:0030426; C:growth cone; ISO:RGD.
DR GO; GO:0014704; C:intercalated disc; IDA:RGD.
DR GO; GO:0030027; C:lamellipodium; IDA:RGD.
DR GO; GO:0016020; C:membrane; IDA:RGD.
DR GO; GO:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell.
DR GO; GO:0031965; C:nuclear membrane; IDA:RGD.
DR GO; GO:0005654; C:nucleoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0014069; C:postsynaptic density; ISO:RGD.
DR GO; GO:0098793; C:presynapse; IEA:GOC.
DR GO; GO:0032991; C:protein-containing complex; ISO:RGD.
DR GO; GO:0001726; C:ruffle; IDA:RGD.
DR GO; GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030018; C:Z disc; IDA:RGD.
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:0004709; F:MAP kinase kinase kinase activity; TAS:RGD.
DR GO; GO:0004672; F:protein kinase activity; IDA:RGD.
DR GO; GO:0019901; F:protein kinase binding; IPI:RGD.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:RGD.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; ISS:UniProtKB.
DR GO; GO:0021764; P:amygdala development; ISO:RGD.
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:RGD.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IDA:RGD.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; ISO:RGD.
DR GO; GO:0021549; P:cerebellum development; IEP:RGD.
DR GO; GO:0006338; P:chromatin remodeling; ISS:UniProtKB.
DR GO; GO:0016358; P:dendrite development; ISO:RGD.
DR GO; GO:0060996; P:dendritic spine development; ISO:RGD.
DR GO; GO:0030010; P:establishment of cell polarity; IMP:RGD.
DR GO; GO:0006887; P:exocytosis; IEA:UniProtKB-KW.
DR GO; GO:0061534; P:gamma-aminobutyric acid secretion, neurotransmission; ISO:RGD.
DR GO; GO:0061535; P:glutamate secretion, neurotransmission; ISO:RGD.
DR GO; GO:0048012; P:hepatocyte growth factor receptor signaling pathway; ISO:RGD.
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; IMP:RGD.
DR GO; GO:0060244; P:negative regulation of cell proliferation involved in contact inhibition; ISS:UniProtKB.
DR GO; GO:0007528; P:neuromuscular junction development; ISO:RGD.
DR GO; GO:0048812; P:neuron projection morphogenesis; IMP:RGD.
DR GO; GO:0098597; P:observational learning; ISO:RGD.
DR GO; GO:0016310; P:phosphorylation; ISO:RGD.
DR GO; GO:0045773; P:positive regulation of axon extension; IMP:RGD.
DR GO; GO:0030335; P:positive regulation of cell migration; ISS:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0010763; P:positive regulation of fibroblast migration; IDA:RGD.
DR GO; GO:0046628; P:positive regulation of insulin receptor signaling pathway; IMP:RGD.
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:RGD.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IMP:RGD.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0090314; P:positive regulation of protein targeting to membrane; IMP:RGD.
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; IMP:RGD.
DR GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; IMP:RGD.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:RGD.
DR GO; GO:0006468; P:protein phosphorylation; IDA:RGD.
DR GO; GO:0043113; P:receptor clustering; ISO:RGD.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; IMP:RGD.
DR GO; GO:0050770; P:regulation of axonogenesis; IBA:GO_Central.
DR GO; GO:0010468; P:regulation of gene expression; ISO:RGD.
DR GO; GO:1900271; P:regulation of long-term synaptic potentiation; ISO:RGD.
DR GO; GO:0043408; P:regulation of MAPK cascade; ISO:RGD.
DR GO; GO:0001666; P:response to hypoxia; IDA:RGD.
DR GO; GO:0010033; P:response to organic substance; IDA:RGD.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; TAS:RGD.
DR GO; GO:0099553; P:trans-synaptic signaling by endocannabinoid, modulating synaptic transmission; ISO:RGD.
DR GO; GO:0019226; P:transmission of nerve impulse; ISO:RGD.
DR GO; GO:0042060; P:wound healing; ISS:UniProtKB.
DR CDD; cd01093; CRIB_PAK_like; 1.
DR Gene3D; 3.90.810.10; -; 1.
DR IDEAL; IID50044; -.
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 3D-structure; Acetylation; Allosteric enzyme; Apoptosis; ATP-binding;
KW Cell junction; Cell membrane; Cell projection; Chromosome; Cytoplasm;
KW Cytoskeleton; 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..544
FT /note="Serine/threonine-protein kinase PAK 1"
FT /id="PRO_0000086462"
FT DOMAIN 75..88
FT /note="CRIB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00057"
FT DOMAIN 269..520
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..79
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 70..140
FT /note="Autoregulatory region"
FT REGION 70..105
FT /note="GTPase-binding"
FT REGION 150..195
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 209..250
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 42..79
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 215..235
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 236..250
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 388
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 275..283
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 298
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:0000269|PubMed:9032240"
FT MOD_RES 57
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000305|PubMed:9032240"
FT MOD_RES 84
FT /note="Phosphothreonine; by OXSR1"
FT /evidence="ECO:0000269|PubMed:14707132"
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:0000305|PubMed:9032240"
FT MOD_RES 149
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000305|PubMed:9032240"
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:0007744|PubMed:22673903"
FT MOD_RES 184
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q13153"
FT MOD_RES 198
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000305|PubMed:9032240"
FT MOD_RES 200
FT /note="Phosphotyrosine; by JAK2"
FT /evidence="ECO:0000250|UniProtKB:Q13153"
FT MOD_RES 203
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:9032240"
FT MOD_RES 211
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q13153"
FT MOD_RES 218
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q13153"
FT MOD_RES 219
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13153"
FT MOD_RES 222
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 224
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O88643"
FT MOD_RES 228
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O88643"
FT MOD_RES 229
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q13153"
FT MOD_RES 284
FT /note="Phosphotyrosine; by JAK2"
FT /evidence="ECO:0000250|UniProtKB:Q13153"
FT MOD_RES 422
FT /note="Phosphothreonine; by autocatalysis, BRSK2 and PDPK1"
FT /evidence="ECO:0000269|PubMed:22669945,
FT ECO:0000269|PubMed:24089484, ECO:0000269|PubMed:9032240"
FT MUTAGEN 83
FT /note="H->L: Abolishes interaction with CDC42, leading to
FT strongly decreased activity; when associated with L-86.
FT Reduces NMDA receptor-mediated synaptic currents; when
FT associated with L-86 and R-299."
FT /evidence="ECO:0000269|PubMed:24089484,
FT ECO:0000269|PubMed:9774440"
FT MUTAGEN 84
FT /note="T->A: Constitutively active."
FT /evidence="ECO:0000269|PubMed:14707132"
FT MUTAGEN 84
FT /note="T->E: Inhibits activation by binding to CDC42."
FT /evidence="ECO:0000269|PubMed:14707132"
FT MUTAGEN 86
FT /note="H->L: Abolishes interaction with CDC42, leading to
FT strongly decreased activity; when associated with L-83.
FT Reduces NMDA receptor-mediated synaptic currents; when
FT associated with L-83 and R-299."
FT /evidence="ECO:0000269|PubMed:24089484,
FT ECO:0000269|PubMed:9774440"
FT MUTAGEN 107
FT /note="L->F: Abolishes autoinhibition, leading to
FT constitutive kinase activation."
FT /evidence="ECO:0000269|PubMed:9774440"
FT MUTAGEN 144
FT /note="S->A: Decreases activity; when associated with A-
FT 149."
FT /evidence="ECO:0000269|PubMed:11278486"
FT MUTAGEN 149
FT /note="S->A: Decreases activity; when associated with A-
FT 144."
FT /evidence="ECO:0000269|PubMed:11278486"
FT MUTAGEN 298
FT /note="K->R: Reduces NMDA receptor-mediated synaptic
FT currents; when associated with L-83 and L-86."
FT /evidence="ECO:0000269|PubMed:24089484"
FT MUTAGEN 404
FT /note="L->S: Decreases kinase activity."
FT /evidence="ECO:0000269|PubMed:9032240"
FT MUTAGEN 422
FT /note="T->A: Decreases activity."
FT /evidence="ECO:0000269|PubMed:11278486,
FT ECO:0000269|PubMed:24089484, ECO:0000269|PubMed:9032240"
FT MUTAGEN 422
FT /note="T->E: Increases constitutive activity."
FT /evidence="ECO:0000269|PubMed:11278486,
FT ECO:0000269|PubMed:24089484, ECO:0000269|PubMed:9032240"
FT STRAND 88..90
FT /evidence="ECO:0007829|PDB:1E0A"
FT HELIX 91..93
FT /evidence="ECO:0007829|PDB:1E0A"
FT STRAND 95..98
FT /evidence="ECO:0007829|PDB:1E0A"
FT HELIX 101..106
FT /evidence="ECO:0007829|PDB:1E0A"
FT STRAND 107..109
FT /evidence="ECO:0007829|PDB:1E0A"
FT STRAND 113..115
FT /evidence="ECO:0007829|PDB:1E0A"
SQ SEQUENCE 544 AA; 60578 MW; 93BE32D8222F5B7B CRC64;
MSNNGLDVQD KPPAPPMRNT STMIGAGSKD PGTLNHGSKP LPPNPEEKKK KDRFYRSILA
GDKTNKKKEK ERPEISLPSD FEHTIHVGFD AVTGEFTGMP EQWARLLQTS NITKSEQKKN
PQAVLDVLEF YNSKKTSNSQ KYMSFTDKSA EDYNSSNTLN VKTVSETPAV PPVSEDEDDD
DDATPPPVIA PRPEHTKSVY TRSVIEPLPV TPTRDVATSP ISPTENNTTP PDALTRNTEK
QKKKPKMSDE EILEKLRSIV SVGDPKKKYT RFEKIGQGAS GTVYTAMDVA TGQEVAIKQM
NLQQQPKKEL IINEILVMRE NKNPNIVNYL DSYLVGDELW VVMEYLAGGS LTDVVTETCM
DEGQIAAVCR ECLQALEFLH SNQVIHRDIK SDNILLGMDG SVKLTDFGFC AQITPEQSKR
STMVGTPYWM APEVVTRKAY GPKVDIWSLG IMAIEMIEGE PPYLNENPLR ALYLIATNGT
PELQNPEKLS AIFRDFLNRC LEMDVEKRGS AKELLQHQFL KIAKPLSSLT PLIAAAKEAT
KNNH
