PAK3_MOUSE
ID PAK3_MOUSE Reviewed; 559 AA.
AC Q61036; O88645; Q8K1R5; Q8K1R6;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2004, sequence version 2.
DT 03-AUG-2022, entry version 203.
DE RecName: Full=Serine/threonine-protein kinase PAK 3;
DE EC=2.7.11.1;
DE AltName: Full=Beta-PAK;
DE AltName: Full=CDC42/RAC effector kinase PAK-B;
DE AltName: Full=p21-activated kinase 3;
DE Short=PAK-3;
GN Name=Pak3; Synonyms=Pak-3, Pakb, Stk4;
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] (ISOFORM 2).
RC TISSUE=Fibroblast;
RX PubMed=7559398; DOI=10.1074/jbc.270.39.22731;
RA Bagrodia S., Taylor S.J., Creasy C.L., Chernoff J., Cerione R.A.;
RT "Identification of a mouse p21Cdc42/Rac activated kinase.";
RL J. Biol. Chem. 270:22731-22737(1995).
RN [2]
RP ERRATUM OF PUBMED:7559398.
RA Bagrodia S., Taylor S.J., Creasy C.L., Chernoff J., Cerione R.A.;
RL J. Biol. Chem. 271:1250-1250(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain;
RX PubMed=12464619; DOI=10.1074/jbc.m207251200;
RA Rousseau V., Goupille O., Morin N., Barnier J.V.;
RT "A new constitutively active brain Pak3 isoform displays modified
RT specificities towards Rac and Cdc42 GTPases.";
RL J. Biol. Chem. 278:3912-3920(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Medulla oblongata;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C3H/He; TISSUE=Mesenchymal stem cell;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP FUNCTION IN PHOSPHORYLATION OF TNNI3.
RX PubMed=12242269; DOI=10.1161/01.res.0000035246.27856.53;
RA Buscemi N., Foster D.B., Neverova I., Van Eyk J.E.;
RT "p21-activated kinase increases the calcium sensitivity of rat triton-
RT skinned cardiac muscle fiber bundles via a mechanism potentially involving
RT novel phosphorylation of troponin I.";
RL Circ. Res. 91:509-516(2002).
RN [8]
RP FUNCTION, AND MUTAGENESIS OF LYS-312.
RX PubMed=15574732; DOI=10.1523/jneurosci.2931-04.2004;
RA Boda B., Alberi S., Nikonenko I., Node-Langlois R., Jourdain P.,
RA Moosmayer M., Parisi-Jourdain L., Muller D.;
RT "The mental retardation protein PAK3 contributes to synapse formation and
RT plasticity in hippocampus.";
RL J. Neurosci. 24:10816-10825(2004).
RN [9]
RP FUNCTION, AND MUTAGENESIS OF HIS-78; HIS-81; LYS-312 AND THR-436.
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 DISRUPTION PHENOTYPE.
RX PubMed=16014725; DOI=10.1523/jneurosci.0028-05.2005;
RA Meng J., Meng Y., Hanna A., Janus C., Jia Z.;
RT "Abnormal long-lasting synaptic plasticity and cognition in mice lacking
RT the mental retardation gene Pak3.";
RL J. Neurosci. 25:6641-6650(2005).
RN [11]
RP FUNCTION, AND MUTAGENESIS OF ARG-67.
RX PubMed=17537723; DOI=10.1074/jbc.m703298200;
RA Kreis P., Thevenot E., Rousseau V., Boda B., Muller D., Barnier J.V.;
RT "The p21-activated kinase 3 implicated in mental retardation regulates
RT spine morphogenesis through a Cdc42-dependent pathway.";
RL J. Biol. Chem. 282:21497-21506(2007).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
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 [13]
RP FUNCTION IN PHOSPHORYLATION OF TNNI3.
RX PubMed=20540949; DOI=10.1016/j.jmb.2010.06.007;
RA Ouyang Y., Mamidi R., Jayasundar J.J., Chandra M., Dong W.J.;
RT "Structural and kinetic effects of PAK3 phosphorylation mimic of
RT cTnI(S151E) on the cTnC-cTnI interaction in the cardiac thin filament.";
RL J. Mol. Biol. 400:1036-1045(2010).
RN [14]
RP DISRUPTION PHENOTYPE.
RX PubMed=21115725; DOI=10.1128/mcb.00969-10;
RA Huang W., Zhou Z., Asrar S., Henkelman M., Xie W., Jia Z.;
RT "p21-Activated kinases 1 and 3 control brain size through coordinating
RT neuronal complexity and synaptic properties.";
RL Mol. Cell. Biol. 31:388-403(2011).
RN [15]
RP FUNCTION.
RX PubMed=25851601; DOI=10.1091/mbc.e14-08-1310;
RA Jaudon F., Raynaud F., Wehrle R., Bellanger J.M., Doulazmi M., Vodjdani G.,
RA Gasman S., Fagni L., Dusart I., Debant A., Schmidt S.;
RT "The RhoGEF DOCK10 is essential for dendritic spine morphogenesis.";
RL Mol. Biol. Cell 26:2112-2127(2015).
RN [16]
RP STRUCTURE BY NMR OF 65-92 AND 108-123 IN COMPLEX WITH CDC42.
RX PubMed=10747784; DOI=10.1021/bi992646d;
RA Gizachew D., Guo W., Chohan K.K., Sutcliffe M.J., Oswald R.E.;
RT "Structure of the complex of Cdc42Hs with a peptide derived from P-21
RT activated kinase.";
RL Biochemistry 39:3963-3971(2000).
CC -!- FUNCTION: Serine/threonine protein kinase that plays a role in a
CC variety of different signaling pathways including cytoskeleton
CC regulation, cell migration, or cell cycle regulation. Plays a role in
CC dendrite spine morphogenesis as well as synapse formation and
CC plasticity (PubMed:25851601). Acts as downstream effector of the small
CC GTPases CDC42 and RAC1. Activation by the binding of active CDC42 and
CC RAC1 results in a conformational change and a subsequent
CC autophosphorylation on several serine and/or threonine residues.
CC Phosphorylates MAPK4 and MAPK6 and activates the downstream target
CC MAPKAPK5, a regulator of F-actin polymerization and cell migration.
CC Additionally, phosphorylates TNNI3/troponin I to modulate calcium
CC sensitivity and relaxation kinetics of thin myofilaments. May also be
CC involved in early neuronal development. In hippocampal neurons,
CC 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). {ECO:0000269|PubMed:12242269,
CC ECO:0000269|PubMed:15574732, ECO:0000269|PubMed:15800193,
CC ECO:0000269|PubMed:17537723, ECO:0000269|PubMed:20540949,
CC ECO:0000269|PubMed:25851601}.
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 -!- 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;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC -!- ACTIVITY REGULATION: Activated by binding small G proteins. Binding of
CC GTP-bound CDC42 or RAC1 to the autoregulatory region releases monomers
CC from the autoinhibited dimer, enables phosphorylation of Thr-436 and
CC allows the kinase domain to adopt an active structure (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: Interacts tightly with GTP-bound but not GDP-bound CDC42/p21
CC and RAC1. Shows highly specific binding to the SH3 domains of
CC phospholipase C-gamma and of adapter protein NCK. Interacts with the C-
CC terminal of APP. Interacts with ARHGEF6 and ARHGEF7 (By similarity).
CC Interacts with GIT1 and GIT2 (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:O75914}.
CC -!- INTERACTION:
CC Q61036; P60953: CDC42; Xeno; NbExp=3; IntAct=EBI-457317, EBI-81752;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q61036-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q61036-2; Sequence=VSP_010243;
CC -!- PTM: Autophosphorylated when activated by CDC42/p21.
CC -!- PTM: Neddylated. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mice show significant abnormalities in synaptic
CC plasticity as well as deficiencies in learning and memory. Pak1 and
CC Pak3 double knockout mice display reduced brains characterized by
CC simplified neuronal dendrites/axons and reduced synapse density.
CC {ECO:0000269|PubMed:16014725, ECO:0000269|PubMed:21115725}.
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; U39738; AAC52354.1; -; mRNA.
DR EMBL; AF082297; AAC31969.1; -; mRNA.
DR EMBL; AJ496262; CAD42790.1; -; mRNA.
DR EMBL; AJ496263; CAD42791.1; -; mRNA.
DR EMBL; AK031853; BAC27580.1; -; mRNA.
DR EMBL; BC053403; AAH53403.1; -; mRNA.
DR CCDS; CCDS30454.1; -. [Q61036-2]
DR CCDS; CCDS57779.1; -. [Q61036-1]
DR PIR; I49376; I49376.
DR RefSeq; NP_001181977.1; NM_001195048.1. [Q61036-1]
DR RefSeq; NP_001181978.1; NM_001195049.1. [Q61036-2]
DR RefSeq; NP_032804.2; NM_008778.3. [Q61036-2]
DR RefSeq; XP_006528815.1; XM_006528752.3. [Q61036-1]
DR RefSeq; XP_006528816.1; XM_006528753.3. [Q61036-2]
DR RefSeq; XP_006528817.1; XM_006528754.3. [Q61036-2]
DR RefSeq; XP_011246092.1; XM_011247790.2. [Q61036-2]
DR RefSeq; XP_017173912.1; XM_017318423.1.
DR PDB; 1EES; NMR; -; B=63-123.
DR PDBsum; 1EES; -.
DR AlphaFoldDB; Q61036; -.
DR SMR; Q61036; -.
DR BioGRID; 202021; 16.
DR DIP; DIP-447N; -.
DR IntAct; Q61036; 6.
DR MINT; Q61036; -.
DR STRING; 10090.ENSMUSP00000108485; -.
DR iPTMnet; Q61036; -.
DR PhosphoSitePlus; Q61036; -.
DR EPD; Q61036; -.
DR jPOST; Q61036; -.
DR MaxQB; Q61036; -.
DR PaxDb; Q61036; -.
DR PRIDE; Q61036; -.
DR ProteomicsDB; 287772; -. [Q61036-1]
DR ProteomicsDB; 287773; -. [Q61036-2]
DR Antibodypedia; 29512; 532 antibodies from 37 providers.
DR DNASU; 18481; -.
DR Ensembl; ENSMUST00000033640; ENSMUSP00000033640; ENSMUSG00000031284. [Q61036-1]
DR Ensembl; ENSMUST00000112863; ENSMUSP00000108484; ENSMUSG00000031284. [Q61036-1]
DR Ensembl; ENSMUST00000112864; ENSMUSP00000108485; ENSMUSG00000031284. [Q61036-2]
DR Ensembl; ENSMUST00000112865; ENSMUSP00000108486; ENSMUSG00000031284. [Q61036-2]
DR Ensembl; ENSMUST00000112868; ENSMUSP00000108489; ENSMUSG00000031284. [Q61036-2]
DR Ensembl; ENSMUST00000172330; ENSMUSP00000126562; ENSMUSG00000031284. [Q61036-2]
DR GeneID; 18481; -.
DR KEGG; mmu:18481; -.
DR UCSC; uc009umg.2; mouse. [Q61036-1]
DR UCSC; uc009umh.2; mouse. [Q61036-2]
DR CTD; 5063; -.
DR MGI; MGI:1339656; Pak3.
DR VEuPathDB; HostDB:ENSMUSG00000031284; -.
DR eggNOG; KOG0578; Eukaryota.
DR GeneTree; ENSGT00950000182988; -.
DR HOGENOM; CLU_000288_26_6_1; -.
DR InParanoid; Q61036; -.
DR OMA; WYDASAT; -.
DR PhylomeDB; Q61036; -.
DR TreeFam; TF105351; -.
DR BRENDA; 2.7.11.1; 3474.
DR Reactome; R-MMU-202433; Generation of second messenger molecules.
DR Reactome; R-MMU-389359; CD28 dependent Vav1 pathway.
DR Reactome; R-MMU-3928664; Ephrin signaling.
DR Reactome; R-MMU-399954; Sema3A PAK dependent Axon repulsion.
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-9013148; CDC42 GTPase cycle.
DR Reactome; R-MMU-9013149; RAC1 GTPase cycle.
DR Reactome; R-MMU-9013409; RHOJ GTPase cycle.
DR Reactome; R-MMU-9013420; RHOU GTPase cycle.
DR BioGRID-ORCS; 18481; 0 hits in 75 CRISPR screens.
DR ChiTaRS; Pak3; mouse.
DR EvolutionaryTrace; Q61036; -.
DR PRO; PR:Q61036; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; Q61036; protein.
DR Bgee; ENSMUSG00000031284; Expressed in ventromedial nucleus of hypothalamus and 186 other tissues.
DR ExpressionAtlas; Q61036; baseline and differential.
DR Genevisible; Q61036; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005768; C:endosome; ISO:MGI.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0014069; C:postsynaptic density; IDA:SynGO.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0051020; F:GTPase binding; ISO:MGI.
DR GO; GO:0004708; F:MAP kinase kinase activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; IDA:MGI.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISO:MGI.
DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW.
DR GO; GO:0031267; F:small GTPase binding; IPI:BHF-UCL.
DR GO; GO:0007409; P:axonogenesis; IMP:UniProtKB.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IDA:MGI.
DR GO; GO:0016358; P:dendrite development; IMP:UniProtKB.
DR GO; GO:0060996; P:dendritic spine development; IGI:MGI.
DR GO; GO:0060997; P:dendritic spine morphogenesis; IMP:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0061003; P:positive regulation of dendritic spine morphogenesis; ISO:MGI.
DR GO; GO:2000573; P:positive regulation of DNA biosynthetic process; ISO:MGI.
DR GO; GO:0010763; P:positive regulation of fibroblast migration; ISO:MGI.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; ISO:MGI.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; ISO:MGI.
DR GO; GO:0030833; P:regulation of actin filament polymerization; ISS:UniProtKB.
DR GO; GO:0050770; P:regulation of axonogenesis; IBA:GO_Central.
DR GO; GO:0043408; P:regulation of MAPK cascade; IBA:GO_Central.
DR GO; GO:0010975; P:regulation of neuron projection development; ISO:MGI.
DR CDD; cd01093; CRIB_PAK_like; 1.
DR CDD; cd06656; STKc_PAK3; 1.
DR Gene3D; 3.90.810.10; -; 1.
DR IDEAL; IID50053; -.
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 InterPro; IPR035063; STK_PAK3.
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; Allosteric enzyme; Alternative splicing; ATP-binding;
KW Cytoplasm; Developmental protein; Kinase; Magnesium; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; SH3-binding; Transferase; Ubl conjugation.
FT CHAIN 1..559
FT /note="Serine/threonine-protein kinase PAK 3"
FT /id="PRO_0000086470"
FT DOMAIN 70..83
FT /note="CRIB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00057"
FT DOMAIN 283..534
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..70
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 65..150
FT /note="Autoregulatory region"
FT /evidence="ECO:0000250"
FT REGION 65..123
FT /note="GTPase-binding"
FT /evidence="ECO:0000250"
FT REGION 84..282
FT /note="Linker"
FT REGION 171..215
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 18..32
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 56..70
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 184..201
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 402
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 289..297
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 312
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305"
FT MOD_RES 2
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q62829"
FT MOD_RES 4
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q62829"
FT MOD_RES 50
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q62829"
FT MOD_RES 154
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q62829"
FT MOD_RES 186
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 436
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q62829"
FT VAR_SEQ 93..107
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10352232,
FT ECO:0000303|PubMed:12464619, ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:7559398"
FT /id="VSP_010243"
FT MUTAGEN 67
FT /note="R->C: Decreases interaction of PAK3 with CDC42 but
FT increases interaction with RAC1."
FT /evidence="ECO:0000269|PubMed:17537723"
FT MUTAGEN 78
FT /note="H->L: When expressed in hippocampal neurons,
FT strongly decreases the number of dendritic spines; when
FT associated with L-81 and R-312."
FT /evidence="ECO:0000269|PubMed:15800193"
FT MUTAGEN 81
FT /note="H->L: When expressed in hippocampal neurons,
FT strongly decreases the number of dendritic spines; when
FT associated with L-78 and R-312."
FT /evidence="ECO:0000269|PubMed:15800193"
FT MUTAGEN 312
FT /note="K->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:15574732"
FT MUTAGEN 312
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 78 and L-81."
FT /evidence="ECO:0000269|PubMed:15800193"
FT MUTAGEN 436
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"
FT CONFLICT 176
FT /note="A -> G (in Ref. 1; AAC52354)"
FT /evidence="ECO:0000305"
FT CONFLICT 286
FT /note="F -> L (in Ref. 1 and 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 376
FT /note="E -> V (in Ref. 1; AAC52354)"
FT /evidence="ECO:0000305"
FT CONFLICT 508
FT /note="R -> H (in Ref. 1; AAC52354)"
FT /evidence="ECO:0000305"
FT CONFLICT 540
FT /note="L -> M (in Ref. 3; AAC31969)"
FT /evidence="ECO:0000305"
FT HELIX 115..118
FT /evidence="ECO:0007829|PDB:1EES"
SQ SEQUENCE 559 AA; 62398 MW; 9AD07B0328F0B08C CRC64;
MSDSLDNEEK PPAPPLRMNS NNRDSSALNH SSKPLPMAPE EKNKKARLRS IFPGGGDKTN
KKKEKERPEI SLPSDFEHTI HVGFDAVTGE FTPDLYGSQM CPGKLPEGIP EQWARLLQTS
NITKLEQKKN PQAVLDVLKF YDSKETVNNQ KYMSFTSGDK SAHGYIAAHQ SNTKTASEPP
LAPPVSEEED EEEEEEEDDN EPPPVIAPRP EHTKSIYTRS VVESIASPAA PNKEDIPPSA
ENANSTTLYR NTDRQRKKSK MTDEEILEKL RSIVSVGDPK KKYTRFEKIG QGASGTVYTA
LDIATGQEVA IKQMNLQQQP KKELIINEIL VMRENKNPNI VNYLDSYLVG DELWVVMEYL
AGGSLTDVVT ETCMDEGQIA AVCRECLQAL DFLHSNQVIH RDIKSDNILL GMDGSVKLTD
FGFCAQITPE QSKRSTMVGT PYWMAPEVVT RKAYGPKVDI WSLGIMAIEM VEGEPPYLNE
NPLRALYLIA TNGTPELQNP ERLSAVFRDF LNRCLEMDVD RRGSAKELLQ HPFLKLAKPL
SSLTPLIIAA KEAIKNSSR
