(data stored in SCRATCH zone)

SWISSPROT: PAK1_HUMAN

ID   PAK1_HUMAN              Reviewed;         545 AA.
AC   Q13153; O75561; Q13567; Q32M53; Q32M54; Q86W79;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   07-MAR-2006, sequence version 2.
DT   11-DEC-2019, entry version 220.
DE   RecName: Full=Serine/threonine-protein kinase PAK 1 {ECO:0000303|PubMed:8805275};
DE            EC=2.7.11.1 {ECO:0000269|PubMed:10551809, ECO:0000269|PubMed:22153498, ECO:0000269|PubMed:9032240};
DE   AltName: Full=Alpha-PAK {ECO:0000303|PubMed:9528787};
DE   AltName: Full=p21-activated kinase 1 {ECO:0000303|PubMed:9395435};
DE            Short=PAK-1;
DE   AltName: Full=p65-PAK {ECO:0000250|UniProtKB:P35465};
GN   Name=PAK1 {ECO:0000312|HGNC:HGNC:8590};
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION.
RC   TISSUE=Placenta;
RX   PubMed=8805275; DOI=10.1016/s0960-9822(02)00546-8;
RA   Brown J.L., Stowers L., Baer M., Trejo J., Coughlin S., Chant J.;
RT   "Human Ste20 homologue hPAK1 links GTPases to the JNK MAP kinase pathway.";
RL   Curr. Biol. 6:598-605(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION.
RX   PubMed=9395435; DOI=10.1016/s0960-9822(97)70091-5;
RA   Sells M.A., Knaus U.G., Bagrodia S., Ambrose D.M., Bokoch G.M.,
RA   Chernoff J.;
RT   "Human p21-activated kinase (Pak1) regulates actin organization in
RT   mammalian cells.";
RL   Curr. Biol. 7:202-210(1997).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA   Reid T., Aspenstroem P., Bertoglio J.;
RT   "Human PAK1B.";
RL   Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16554811; DOI=10.1038/nature04632;
RA   Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA   Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA   Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA   Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA   Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA   Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT   "Human chromosome 11 DNA sequence and analysis including novel gene
RT   identification.";
RL   Nature 440:497-500(2006).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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   [6]
RP   FUNCTION, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, ACTIVITY REGULATION, AND
RP   SUBCELLULAR LOCATION.
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   [7]
RP   MUTAGENESIS OF HIS-83 AND HIS-86.
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, 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   INTERACTION WITH NCK1 AND NCK2.
RX   PubMed=10026169; DOI=10.1074/jbc.274.9.5542;
RA   Braverman L.E., Quilliam L.A.;
RT   "Identification of Grb4/Nckbeta, a src homology 2 and 3 domain-containing
RT   adapter protein having similar binding and biological properties to Nck.";
RL   J. Biol. Chem. 274:5542-5549(1999).
RN   [10]
RP   CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, AUTOREGULATORY REGION, FUNCTION,
RP   INTERACTION WITH CDC42, PHOSPHORYLATION AT THR-423, AND MUTAGENESIS OF
RP   HIS-83; HIS-86; LEU-107 AND THR-423.
RX   PubMed=10551809; DOI=10.1074/jbc.274.46.32565;
RA   Zenke F.T., King C.C., Bohl B.P., Bokoch G.M.;
RT   "Identification of a central phosphorylation site in p21-activated kinase
RT   regulating autoinhibition and kinase activity.";
RL   J. Biol. Chem. 274:32565-32573(1999).
RN   [11]
RP   PHOSPHORYLATION AT THR-423 BY PDPK1, INTERACTION WITH PDPK1, AND ACTIVITY
RP   REGULATION.
RX   PubMed=10995762; DOI=10.1074/jbc.m006553200;
RA   King C.C., Gardiner E.M., Zenke F.T., Bohl B.P., Newton A.C.,
RA   Hemmings B.A., Bokoch G.M.;
RT   "p21-activated kinase (PAK1) is phosphorylated and activated by 3-
RT   phosphoinositide-dependent kinase-1 (PDK1).";
RL   J. Biol. Chem. 275:41201-41209(2000).
RN   [12]
RP   FUNCTION IN PHOSPHORYLATION OF RAF1, AND INTERACTION WITH RAF1.
RX   PubMed=11733498; DOI=10.1074/jbc.m110000200;
RA   Zang M., Hayne C., Luo Z.;
RT   "Interaction between active Pak1 and Raf-1 is necessary for phosphorylation
RT   and activation of Raf-1.";
RL   J. Biol. Chem. 277:4395-4405(2002).
RN   [13]
RP   SUBUNIT, AND ACTIVITY REGULATION.
RX   PubMed=11804587; DOI=10.1016/s1097-2765(01)00428-2;
RA   Parrini M.C., Lei M., Harrison S.C., Mayer B.J.;
RT   "Pak1 kinase homodimers are autoinhibited in trans and dissociated upon
RT   activation by Cdc42 and Rac1.";
RL   Mol. Cell 9:73-83(2002).
RN   [14]
RP   FUNCTION, AND INTERACTION WITH CDC2L1 AND CDC2L2.
RX   PubMed=12624090; DOI=10.1074/jbc.m300818200;
RA   Chen S., Yin X., Zhu X., Yan J., Ji S., Chen C., Cai M., Zhang S., Zong H.,
RA   Hu Y., Yuan Z., Shen Z., Gu J.;
RT   "The C-terminal kinase domain of the p34cdc2-related PITSLRE protein kinase
RT   (p110C) associates with p21-activated kinase 1 and inhibits its activity
RT   during anoikis.";
RL   J. Biol. Chem. 278:20029-20036(2003).
RN   [15]
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   [16]
RP   PHOSPHORYLATION AT SER-21, IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION,
RP   INTERACTION WITH NCK1, AND SUBCELLULAR LOCATION.
RX   PubMed=14585966; DOI=10.1128/mcb.23.22.8058-8069.2003;
RA   Zhou G.L., Zhuo Y., King C.C., Fryer B.H., Bokoch G.M., Field J.;
RT   "Akt phosphorylation of serine 21 on Pak1 modulates Nck binding and cell
RT   migration.";
RL   Mol. Cell. Biol. 23:8058-8069(2003).
RN   [17]
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   [18]
RP   FUNCTION, AND INTERACTION WITH SNAI1.
RX   PubMed=15833848; DOI=10.1158/0008-5472.can-04-3480;
RA   Yang Z., Rayala S., Nguyen D., Vadlamudi R.K., Chen S., Kumar R.;
RT   "Pak1 phosphorylation of snail, a master regulator of epithelial-to-
RT   mesenchyme transition, modulates snail's subcellular localization and
RT   functions.";
RL   Cancer Res. 65:3179-3184(2005).
RN   [19]
RP   FUNCTION.
RX   PubMed=15611088; DOI=10.1074/jbc.m411900200;
RA   Zhou H., Kramer R.H.;
RT   "Integrin engagement differentially modulates epithelial cell motility by
RT   RhoA/ROCK and PAK1.";
RL   J. Biol. Chem. 280:10624-10635(2005).
RN   [20]
RP   INTERACTION WITH CIB1, AND SUBCELLULAR LOCATION.
RX   PubMed=16061695; DOI=10.1083/jcb.200502090;
RA   Leisner T.M., Liu M., Jaffer Z.M., Chernoff J., Parise L.V.;
RT   "Essential role of CIB1 in regulating PAK1 activation and cell migration.";
RL   J. Cell Biol. 170:465-476(2005).
RN   [21]
RP   FUNCTION, AND INTERACTION WITH TBCB.
RX   PubMed=15831477; DOI=10.1128/mcb.25.9.3726-3736.2005;
RA   Vadlamudi R.K., Barnes C.J., Rayala S., Li F., Balasenthil S., Marcus S.,
RA   Goodson H.V., Sahin A.A., Kumar R.;
RT   "p21-activated kinase 1 regulates microtubule dynamics by phosphorylating
RT   tubulin cofactor B.";
RL   Mol. Cell. Biol. 25:3726-3736(2005).
RN   [22]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-212, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=16964243; DOI=10.1038/nbt1240;
RA   Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT   "A probability-based approach for high-throughput protein phosphorylation
RT   analysis and site localization.";
RL   Nat. Biotechnol. 24:1285-1292(2006).
RN   [23]
RP   FUNCTION, AND INTERACTION WITH CRIPAK.
RX   PubMed=16278681; DOI=10.1038/sj.onc.1209172;
RA   Talukder A.H., Meng Q., Kumar R.;
RT   "CRIPak, a novel endogenous Pak1 inhibitor.";
RL   Oncogene 25:1311-1319(2006).
RN   [24]
RP   FUNCTION, PHOSPHORYLATION AT TYR-153; TYR-201 AND TYR-285, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY.
RX   PubMed=17726028; DOI=10.1074/jbc.m701794200;
RA   Rider L., Shatrova A., Feener E.P., Webb L., Diakonova M.;
RT   "JAK2 tyrosine kinase phosphorylates PAK1 and regulates PAK1 activity and
RT   functions.";
RL   J. Biol. Chem. 282:30985-30996(2007).
RN   [25]
RP   FUNCTION, PHOSPHORYLATION AT SER-21; SER-57; TYR-131; TYR-142; TYR-153;
RP   SER-174; THR-185; THR-212 AND TYR-285, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY.
RX   PubMed=17989089; DOI=10.1242/jcs.008177;
RA   Mayhew M.W., Jeffery E.D., Sherman N.E., Nelson K., Polefrone J.M.,
RA   Pratt S.J., Shabanowitz J., Parsons J.T., Fox J.W., Hunt D.F.,
RA   Horwitz A.F.;
RT   "Identification of phosphorylation sites in betaPIX and PAK1.";
RL   J. Cell Sci. 120:3911-3918(2007).
RN   [26]
RP   INTERACTION WITH RAC1 AND CDC42.
RX   PubMed=18325335; DOI=10.1016/j.febslet.2008.01.064;
RA   Matsuda C., Kameyama K., Suzuki A., Mishima W., Yamaji S., Okamoto H.,
RA   Nishino I., Hayashi Y.K.;
RT   "Affixin activates Rac1 via betaPIX in C2C12 myoblast.";
RL   FEBS Lett. 582:1189-1196(2008).
RN   [27]
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   [28]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-230, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA   Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA   Elledge S.J., Gygi S.P.;
RT   "A quantitative atlas of mitotic phosphorylation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN   [29]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19413330; DOI=10.1021/ac9004309;
RA   Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT   "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT   refined SCX-based approach.";
RL   Anal. Chem. 81:4493-4501(2009).
RN   [30]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-204; THR-212; THR-219;
RP   SER-220 AND THR-230, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP   ANALYSIS].
RC   TISSUE=Leukemic T-cell;
RX   PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA   Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA   Rodionov V., Han D.K.;
RT   "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT   reveals system-wide modulation of protein-protein interactions.";
RL   Sci. Signal. 2:RA46-RA46(2009).
RN   [31]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [32]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-144; SER-149; SER-174;
RP   SER-223 AND THR-230, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP   ANALYSIS].
RX   PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA   Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA   Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT   "System-wide temporal characterization of the proteome and phosphoproteome
RT   of human embryonic stem cell differentiation.";
RL   Sci. Signal. 4:RS3-RS3(2011).
RN   [33]
RP   FUNCTION, SUBCELLULAR LOCATION, AND PHOSPHORYLATION AT THR-212.
RX   PubMed=23260667; DOI=10.1016/j.celrep.2012.11.018;
RA   Li D.Q., Nair S.S., Ohshiro K., Kumar A., Nair V.S., Pakala S.B.,
RA   Reddy S.D., Gajula R.P., Eswaran J., Aravind L., Kumar R.;
RT   "MORC2 signaling integrates phosphorylation-dependent, ATPase-coupled
RT   chromatin remodeling during the DNA damage response.";
RL   Cell Rep. 2:1657-1669(2012).
RN   [34]
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   [35]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP   METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP   [LARGE SCALE ANALYSIS].
RX   PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA   Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA   Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA   Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT   "N-terminal acetylome analyses and functional insights of the N-terminal
RT   acetyltransferase NatB.";
RL   Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN   [36]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-230, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma, and Erythroleukemia;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
RN   [37]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-115, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [38]
RP   INTERACTION WITH CIB1 ISOFORM 2.
RC   TISSUE=Brain;
RX   PubMed=23503467; DOI=10.1038/onc.2013.43;
RA   Armacki M., Joodi G., Nimmagadda S.C., de Kimpe L., Pusapati G.V.,
RA   Vandoninck S., Van Lint J., Illing A., Seufferlein T.;
RT   "A novel splice variant of calcium and integrin-binding protein 1 mediates
RT   protein kinase D2-stimulated tumour growth by regulating angiogenesis.";
RL   Oncogene 33:1167-1180(2014).
RN   [39]
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).
RN   [40]
RP   FUNCTION, COLOCALIZATION WITH RUFY3, SUBCELLULAR LOCATION, AND TISSUE
RP   SPECIFICITY.
RX   PubMed=25766321; DOI=10.1038/cddis.2015.50;
RA   Wang G., Zhang Q., Song Y., Wang X., Guo Q., Zhang J., Li J., Han Y.,
RA   Miao Z., Li F.;
RT   "PAK1 regulates RUFY3-mediated gastric cancer cell migration and
RT   invasion.";
RL   Cell Death Dis. 6:E1682-E1682(2015).
RN   [41]
RP   INTERACTION WITH INPP5K.
RX   PubMed=26940976; DOI=10.1111/gtc.12353;
RA   Ijuin T., Hatano N., Takenawa T.;
RT   "Glucose-regulated protein 78 (GRP78) binds directly to PIP3 phosphatase
RT   SKIP and determines its localization.";
RL   Genes Cells 21:457-465(2016).
RN   [42]
RP   INVOLVEMENT IN IDDMSSD, VARIANTS IDDMSSD CYS-131 AND CYS-429,
RP   CHARACTERIZATION OF VARIANTS IDDMSSD CYS-131 AND CYS-429, FUNCTION, AND
RP   HOMODIMERIZATION.
RX   PubMed=30290153; DOI=10.1016/j.ajhg.2018.09.005;
RA   Harms F.L., Kloth K., Bley A., Denecke J., Santer R., Lessel D., Hempel M.,
RA   Kutsche K.;
RT   "Activating mutations in PAK1, encoding p21-activated kinase 1, cause a
RT   neurodevelopmental disorder.";
RL   Am. J. Hum. Genet. 103:579-591(2018).
RN   [43]
RP   X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 70-545.
RX   PubMed=10975528; DOI=10.1016/s0092-8674(00)00043-x;
RA   Lei M., Lu W., Meng W., Parrini M.C., Eck M.J., Mayer B.J., Harrison S.C.;
RT   "Structure of PAK1 in an autoinhibited conformation reveals a multistage
RT   activation switch.";
RL   Cell 102:387-397(2000).
RN   [44]
RP   STRUCTURE BY NMR OF 183-204 IN COMPLEX WITH ARHGEF7, AND INTERACTION WITH
RP   ARHGEF7.
RX   PubMed=16101281; DOI=10.1021/bi050374a;
RA   Mott H.R., Nietlispach D., Evetts K.A., Owen D.;
RT   "Structural analysis of the SH3 domain of beta-PIX and its interaction with
RT   alpha-p21 activated kinase (PAK).";
RL   Biochemistry 44:10977-10983(2005).
RN   [45]
RP   X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 249-545, AND ACTIVITY REGULATION.
RX   PubMed=15893667; DOI=10.1016/j.str.2005.03.007;
RA   Lei M., Robinson M.A., Harrison S.C.;
RT   "The active conformation of the PAK1 kinase domain.";
RL   Structure 13:769-778(2005).
RN   [46]
RP   X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 248-545 OF MUTANT ARG-299 IN
RP   COMPLEX WITH ATP ANALOG AMP-PNP, MUTAGENESIS OF LYS-299 AND ASP-389,
RP   CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, SUBUNIT, AND PHOSPHORYLATION AT
RP   THR-423.
RX   PubMed=22153498; DOI=10.1016/j.str.2011.10.013;
RA   Wang J., Wu J.W., Wang Z.X.;
RT   "Structural insights into the autoactivation mechanism of p21-activated
RT   protein kinase.";
RL   Structure 19:1752-1761(2011).
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 (PubMed:30290153). Can directly phosphorylate BAD and
CC       protects cells against apoptosis. Activated by interaction with CDC42
CC       and RAC1. Functions as GTPase effector that links the Rho-related
CC       GTPases CDC42 and RAC1 to the JNK MAP kinase pathway. Phosphorylates
CC       and activates MAP2K1, and thereby mediates activation of downstream MAP
CC       kinases. Involved in the reorganization of the actin cytoskeleton,
CC       actin stress fibers and of focal adhesion complexes. Phosphorylates the
CC       tubulin chaperone TBCB and thereby plays a role in the regulation of
CC       microtubule biogenesis and organization of the tubulin cytoskeleton.
CC       Plays a role in the regulation of insulin secretion in response to
CC       elevated glucose levels. Part of a ternary complex that contains PAK1,
CC       DVL1 and MUSK that is important for MUSK-dependent regulation of AChR
CC       clustering during the formation of the neuromuscular junction (NMJ).
CC       Activity is inhibited in cells undergoing apoptosis, potentially due to
CC       binding of CDC2L1 and CDC2L2. Phosphorylates MYL9/MLC2. Phosphorylates
CC       RAF1 at 'Ser-338' and 'Ser-339' resulting in: activation of RAF1,
CC       stimulation of RAF1 translocation to mitochondria, phosphorylation of
CC       BAD by RAF1, and RAF1 binding to BCL2. Phosphorylates SNAI1 at 'Ser-
CC       246' promoting its transcriptional repressor activity by increasing its
CC       accumulation in the nucleus. In podocytes, promotes NR3C2 nuclear
CC       localization. Required for atypical chemokine receptor ACKR2-induced
CC       phosphorylation of LIMK1 and cofilin (CFL1) and for the up-regulation
CC       of ACKR2 from endosomal compartment to cell membrane, increasing its
CC       efficiency in chemokine uptake and degradation. In synapses, seems to
CC       mediate the regulation of F-actin cluster formation performed by
CC       SHANK3, maybe through CFL1 phosphorylation and inactivation. Plays a
CC       role in RUFY3-mediated facilitating gastric cancer cells migration and
CC       invasion (PubMed:25766321). In response to DNA damage, phosphorylates
CC       MORC2 which activates its ATPase activity and facilitates chromatin
CC       remodeling (PubMed:23260667). {ECO:0000269|PubMed:10551809,
CC       ECO:0000269|PubMed:11733498, ECO:0000269|PubMed:12624090,
CC       ECO:0000269|PubMed:12876277, ECO:0000269|PubMed:14585966,
CC       ECO:0000269|PubMed:15611088, ECO:0000269|PubMed:15831477,
CC       ECO:0000269|PubMed:15833848, ECO:0000269|PubMed:16278681,
CC       ECO:0000269|PubMed:17726028, ECO:0000269|PubMed:17989089,
CC       ECO:0000269|PubMed:22669945, ECO:0000269|PubMed:23260667,
CC       ECO:0000269|PubMed:23633677, ECO:0000269|PubMed:25766321,
CC       ECO:0000269|PubMed:30290153, ECO:0000269|PubMed:8805275,
CC       ECO:0000269|PubMed:9032240, ECO:0000269|PubMed:9395435,
CC       ECO:0000269|PubMed:9528787}.
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:10551809, ECO:0000269|PubMed:22153498,
CC         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:10551809,
CC         ECO:0000269|PubMed:22153498, 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-423. {ECO:0000250|UniProtKB:P35465,
CC       ECO:0000269|PubMed:10995762, ECO:0000269|PubMed:11804587,
CC       ECO:0000269|PubMed:15893667, ECO:0000269|PubMed:9032240}.
CC   -!- SUBUNIT: Homodimer; homodimerization results in autoinhibition
CC       (PubMed:30290153). Active as monomer. Component of cytoplasmic
CC       complexes, which also contains PXN, ARHGEF6 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 (PubMed:12624090).
CC       Interacts with ARHGEF7 (PubMed:16101281). Interacts tightly with GTP-
CC       bound but not GDP-bound CDC42/P21 and RAC1 (By similarity). Probably
CC       found in a ternary complex composed of DSCAM, PAK1 and RAC1. Interacts
CC       with DSCAM (via cytoplasmic domain); the interaction is direct and
CC       enhanced in presence of RAC1 (PubMed:15169762). Interacts with SCRIB
CC       (PubMed:18716323). Interacts with PDPK1 (PubMed:10995762). Interacts
CC       (via kinase domain) with RAF1 (PubMed:11733498). Interacts with NCK1
CC       and NCK2 (PubMed:10026169). Interacts with TBCB (PubMed:15831477).
CC       Interacts with CRIPAK (PubMed:16278681). Interacts with BRSK2 (By
CC       similarity). Interacts with SNAI1 (PubMed:15833848). Interacts with
CC       CIB1 isoform 2 (PubMed:23503467). Interacts with CIB1 (via N-terminal
CC       region); the interaction is direct, promotes PAK1 activity and occurs
CC       in a calcium-dependent manner. Interacts with INPP5K (PubMed:26940976).
CC       {ECO:0000250|UniProtKB:O88643, ECO:0000250|UniProtKB:P35465,
CC       ECO:0000269|PubMed:10026169, ECO:0000269|PubMed:10551809,
CC       ECO:0000269|PubMed:10995762, ECO:0000269|PubMed:11733498,
CC       ECO:0000269|PubMed:11804587, ECO:0000269|PubMed:12624090,
CC       ECO:0000269|PubMed:14585966, ECO:0000269|PubMed:15169762,
CC       ECO:0000269|PubMed:15831477, ECO:0000269|PubMed:15833848,
CC       ECO:0000269|PubMed:16061695, ECO:0000269|PubMed:16101281,
CC       ECO:0000269|PubMed:16278681, ECO:0000269|PubMed:18325335,
CC       ECO:0000269|PubMed:18716323, ECO:0000269|PubMed:22153498,
CC       ECO:0000269|PubMed:22669945, ECO:0000269|PubMed:23503467,
CC       ECO:0000269|PubMed:26940976, ECO:0000269|PubMed:30290153}.
CC   -!- INTERACTION:
CC       Q14155:ARHGEF7; NbExp=9; IntAct=EBI-1307, EBI-717515;
CC       P60953:CDC42; NbExp=12; IntAct=EBI-1307, EBI-81752;
CC       P60766:Cdc42 (xeno); NbExp=3; IntAct=EBI-1307, EBI-81763;
CC       P21127:CDK11B; NbExp=4; IntAct=EBI-1307, EBI-1298;
CC       Q8N1N5:CRIPAK; NbExp=6; IntAct=EBI-1307, EBI-1205846;
CC       Q9Y2X7:GIT1; NbExp=3; IntAct=EBI-1307, EBI-466061;
CC       P53667:LIMK1; NbExp=5; IntAct=EBI-1307, EBI-444403;
CC       O43639:NCK2; NbExp=6; IntAct=EBI-1307, EBI-713635;
CC       Q15365:PCBP1; NbExp=5; IntAct=EBI-15628682, EBI-946095;
CC       P63000:RAC1; NbExp=25; IntAct=EBI-1307, EBI-413628;
CC       P63000-1:RAC1; NbExp=3; IntAct=EBI-1307, EBI-7212896;
CC       P63001:Rac1 (xeno); NbExp=3; IntAct=EBI-1307, EBI-413646;
CC       Q7L0Q8:RHOU; NbExp=2; IntAct=EBI-1019502, EBI-1638043;
CC       Q5PP90:US3(L) (xeno); NbExp=2; IntAct=EBI-1307, EBI-15780451;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:23260667,
CC       ECO:0000269|PubMed:25766321}. Cell junction, focal adhesion
CC       {ECO:0000269|PubMed:25766321}. Cell membrane
CC       {ECO:0000269|PubMed:25766321}. Cell projection, ruffle membrane
CC       {ECO:0000269|PubMed:25766321}. Cell projection, invadopodium
CC       {ECO:0000269|PubMed:25766321}. Nucleus, nucleoplasm
CC       {ECO:0000269|PubMed:23260667}. Chromosome
CC       {ECO:0000269|PubMed:23260667}. Note=Colocalizes with RUFY3, F-actin and
CC       other core migration components in invadopodia at the cell periphery
CC       (PubMed:25766321). Recruited to the cell membrane by interaction with
CC       CDC42 and RAC1. Recruited to focal adhesions upon activation.
CC       Colocalized with CIB1 within membrane ruffles during cell spreading
CC       upon readhesion to fibronectin. Upon DNA damage, translocates to the
CC       nucleoplasm when phosphorylated at Thr-212 where is co-recruited with
CC       MORC2 on damaged chromatin (PubMed:23260667).
CC       {ECO:0000250|UniProtKB:P35465, ECO:0000269|PubMed:23260667,
CC       ECO:0000269|PubMed:25766321}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q13153-1; Sequence=Displayed;
CC       Name=2; Synonyms=PAK1B;
CC         IsoId=Q13153-2; Sequence=VSP_017507;
CC   -!- TISSUE SPECIFICITY: Overexpressed in gastric cancer cells and tissues
CC       (at protein level) (PubMed:25766321). {ECO:0000269|PubMed:25766321}.
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. Upon DNA damage, phosphorylated at Thr-212 and
CC       translocates to the nucleoplasm (PubMed:23260667). Phosphorylated at
CC       tyrosine residues, which can be enhanced by NTN1 (By similarity).
CC       {ECO:0000250|UniProtKB:O88643, ECO:0000269|PubMed:10551809,
CC       ECO:0000269|PubMed:10995762, ECO:0000269|PubMed:14585966,
CC       ECO:0000269|PubMed:17726028, ECO:0000269|PubMed:17989089,
CC       ECO:0000269|PubMed:22153498, ECO:0000269|PubMed:22669945,
CC       ECO:0000269|PubMed:23260667, ECO:0000269|PubMed:23633677}.
CC   -!- DISEASE: Intellectual developmental disorder with macrocephaly,
CC       seizures, and speech delay (IDDMSSD) [MIM:618158]: An autosomal
CC       dominant neurodevelopmental disorder characterized by impaired
CC       intellectual development, poor speech, postnatal macrocephaly, and
CC       seizures. {ECO:0000269|PubMed:30290153}. Note=The disease is caused by
CC       mutations affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC       protein kinase family. STE20 subfamily. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC       Haematology;
CC       URL="http://atlasgeneticsoncology.org/Genes/PAK1ID41633ch11q13.html";
DR   EMBL; U51120; AAC50590.1; -; mRNA.
DR   EMBL; U24152; AAA65441.1; -; mRNA.
DR   EMBL; AF071884; AAC24716.1; -; mRNA.
DR   EMBL; AP000486; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AP003680; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC109299; AAI09300.1; -; mRNA.
DR   CCDS; CCDS44687.1; -. [Q13153-2]
DR   CCDS; CCDS8250.1; -. [Q13153-1]
DR   PIR; G01773; G01773.
DR   RefSeq; NP_001122092.1; NM_001128620.1. [Q13153-2]
DR   RefSeq; NP_002567.3; NM_002576.4. [Q13153-1]
DR   RefSeq; XP_011543382.1; XM_011545080.2. [Q13153-2]
DR   RefSeq; XP_011543383.1; XM_011545081.2. [Q13153-2]
DR   RefSeq; XP_011543384.1; XM_011545082.2. [Q13153-2]
DR   RefSeq; XP_011543385.1; XM_011545083.2. [Q13153-2]
DR   RefSeq; XP_011543386.1; XM_011545084.2. [Q13153-2]
DR   RefSeq; XP_016873335.1; XM_017017846.1. [Q13153-1]
DR   RefSeq; XP_016873336.1; XM_017017847.1. [Q13153-1]
DR   RefSeq; XP_016873337.1; XM_017017848.1. [Q13153-1]
DR   RefSeq; XP_016873338.1; XM_017017849.1. [Q13153-1]
DR   RefSeq; XP_016873339.1; XM_017017850.1. [Q13153-1]
DR   PDB; 1F3M; X-ray; 2.30 A; A/B=70-149, C/D=249-545.
DR   PDB; 1YHV; X-ray; 1.80 A; A=249-545.
DR   PDB; 1YHW; X-ray; 1.80 A; A=249-545.
DR   PDB; 1ZSG; NMR; -; B=183-204.
DR   PDB; 2HY8; X-ray; 2.00 A; 1=249-545.
DR   PDB; 2QME; X-ray; 1.75 A; I=74-109.
DR   PDB; 3DVP; X-ray; 2.50 A; C/D=212-221.
DR   PDB; 3FXZ; X-ray; 1.64 A; A=249-545.
DR   PDB; 3FY0; X-ray; 2.35 A; A=249-545.
DR   PDB; 3Q4Z; X-ray; 1.89 A; A/B=248-545.
DR   PDB; 3Q52; X-ray; 1.80 A; A=248-545.
DR   PDB; 3Q53; X-ray; 2.09 A; A=248-545.
DR   PDB; 4DAW; X-ray; 2.00 A; A=249-545.
DR   PDB; 4EQC; X-ray; 2.01 A; A=249-545.
DR   PDB; 4O0R; X-ray; 2.40 A; A/B=249-545.
DR   PDB; 4O0T; X-ray; 2.60 A; A/B=249-545.
DR   PDB; 4P90; X-ray; 2.49 A; A/B=249-545.
DR   PDB; 4ZJI; X-ray; 1.99 A; A/B/C/D=249-545.
DR   PDB; 4ZJJ; X-ray; 2.20 A; A/B/C/D=249-545.
DR   PDB; 4ZLO; X-ray; 2.50 A; A/B=249-545.
DR   PDB; 4ZY4; X-ray; 2.60 A; A/B=249-545.
DR   PDB; 4ZY5; X-ray; 2.35 A; A/B=249-545.
DR   PDB; 4ZY6; X-ray; 2.15 A; A/B=249-545.
DR   PDB; 5DEW; X-ray; 1.90 A; A/B=249-545.
DR   PDB; 5DEY; X-ray; 2.10 A; A/B=249-545.
DR   PDB; 5DFP; X-ray; 2.20 A; A=249-545.
DR   PDB; 5IME; X-ray; 2.22 A; A/B=249-545.
DR   PDB; 5KBQ; X-ray; 2.58 A; A/B=254-542.
DR   PDB; 5KBR; X-ray; 2.36 A; A/B=254-542.
DR   PDB; 6B16; X-ray; 2.29 A; A/B=249-545.
DR   PDBsum; 1F3M; -.
DR   PDBsum; 1YHV; -.
DR   PDBsum; 1YHW; -.
DR   PDBsum; 1ZSG; -.
DR   PDBsum; 2HY8; -.
DR   PDBsum; 2QME; -.
DR   PDBsum; 3DVP; -.
DR   PDBsum; 3FXZ; -.
DR   PDBsum; 3FY0; -.
DR   PDBsum; 3Q4Z; -.
DR   PDBsum; 3Q52; -.
DR   PDBsum; 3Q53; -.
DR   PDBsum; 4DAW; -.
DR   PDBsum; 4EQC; -.
DR   PDBsum; 4O0R; -.
DR   PDBsum; 4O0T; -.
DR   PDBsum; 4P90; -.
DR   PDBsum; 4ZJI; -.
DR   PDBsum; 4ZJJ; -.
DR   PDBsum; 4ZLO; -.
DR   PDBsum; 4ZY4; -.
DR   PDBsum; 4ZY5; -.
DR   PDBsum; 4ZY6; -.
DR   PDBsum; 5DEW; -.
DR   PDBsum; 5DEY; -.
DR   PDBsum; 5DFP; -.
DR   PDBsum; 5IME; -.
DR   PDBsum; 5KBQ; -.
DR   PDBsum; 5KBR; -.
DR   PDBsum; 6B16; -.
DR   SMR; Q13153; -.
DR   BioGrid; 111095; 93.
DR   CORUM; Q13153; -.
DR   DIP; DIP-31016N; -.
DR   ELM; Q13153; -.
DR   IntAct; Q13153; 75.
DR   MINT; Q13153; -.
DR   STRING; 9606.ENSP00000278568; -.
DR   BindingDB; Q13153; -.
DR   ChEMBL; CHEMBL4600; -.
DR   DrugBank; DB12010; Fostamatinib.
DR   DrugCentral; Q13153; -.
DR   GuidetoPHARMACOLOGY; 2133; -.
DR   MoonDB; Q13153; Predicted.
DR   iPTMnet; Q13153; -.
DR   PhosphoSitePlus; Q13153; -.
DR   BioMuta; PAK1; -.
DR   DMDM; 90111767; -.
DR   EPD; Q13153; -.
DR   jPOST; Q13153; -.
DR   MassIVE; Q13153; -.
DR   MaxQB; Q13153; -.
DR   PaxDb; Q13153; -.
DR   PeptideAtlas; Q13153; -.
DR   PRIDE; Q13153; -.
DR   ProteomicsDB; 59193; -. [Q13153-1]
DR   ProteomicsDB; 59194; -. [Q13153-2]
DR   DNASU; 5058; -.
DR   Ensembl; ENST00000278568; ENSP00000278568; ENSG00000149269. [Q13153-2]
DR   Ensembl; ENST00000356341; ENSP00000348696; ENSG00000149269. [Q13153-1]
DR   GeneID; 5058; -.
DR   KEGG; hsa:5058; -.
DR   UCSC; uc001oyg.5; human. [Q13153-1]
DR   CTD; 5058; -.
DR   DisGeNET; 5058; -.
DR   EuPathDB; HostDB:ENSG00000149269.9; -.
DR   GeneCards; PAK1; -.
DR   HGNC; HGNC:8590; PAK1.
DR   HPA; CAB005312; -.
DR   HPA; HPA003565; -.
DR   MalaCards; PAK1; -.
DR   MIM; 602590; gene.
DR   MIM; 618158; phenotype.
DR   neXtProt; NX_Q13153; -.
DR   OpenTargets; ENSG00000149269; -.
DR   PharmGKB; PA32917; -.
DR   eggNOG; KOG0578; Eukaryota.
DR   eggNOG; ENOG410XP4K; LUCA.
DR   GeneTree; ENSGT00950000182988; -.
DR   HOGENOM; HOG000234202; -.
DR   InParanoid; Q13153; -.
DR   KO; K04409; -.
DR   OMA; TKMVGVV; -.
DR   OrthoDB; 757766at2759; -.
DR   PhylomeDB; Q13153; -.
DR   TreeFam; TF105351; -.
DR   BRENDA; 2.7.11.1; 2681.
DR   Reactome; R-HSA-202433; Generation of second messenger molecules.
DR   Reactome; R-HSA-2029482; Regulation of actin dynamics for phagocytic cup formation.
DR   Reactome; R-HSA-2871796; FCERI mediated MAPK activation.
DR   Reactome; R-HSA-376172; DSCAM interactions.
DR   Reactome; R-HSA-389359; CD28 dependent Vav1 pathway.
DR   Reactome; R-HSA-3928662; EPHB-mediated forward signaling.
DR   Reactome; R-HSA-3928664; Ephrin signaling.
DR   Reactome; R-HSA-399954; Sema3A PAK dependent Axon repulsion.
DR   Reactome; R-HSA-428540; Activation of RAC1.
DR   Reactome; R-HSA-445144; Signal transduction by L1.
DR   Reactome; R-HSA-445355; Smooth Muscle Contraction.
DR   Reactome; R-HSA-5218920; VEGFR2 mediated vascular permeability.
DR   Reactome; R-HSA-5621575; CD209 (DC-SIGN) signaling.
DR   Reactome; R-HSA-5625740; RHO GTPases activate PKNs.
DR   Reactome; R-HSA-5627117; RHO GTPases Activate ROCKs.
DR   Reactome; R-HSA-5627123; RHO GTPases activate PAKs.
DR   Reactome; R-HSA-5687128; MAPK6/MAPK4 signaling.
DR   Reactome; R-HSA-8964616; G beta:gamma signalling through CDC42.
DR   SignaLink; Q13153; -.
DR   SIGNOR; Q13153; -.
DR   ChiTaRS; PAK1; human.
DR   EvolutionaryTrace; Q13153; -.
DR   GeneWiki; PAK1; -.
DR   GenomeRNAi; 5058; -.
DR   Pharos; Q13153; Tchem.
DR   PRO; PR:Q13153; -.
DR   Proteomes; UP000005640; Chromosome 11.
DR   RNAct; Q13153; protein.
DR   Bgee; ENSG00000149269; Expressed in 203 organ(s), highest expression level in middle temporal gyrus.
DR   ExpressionAtlas; Q13153; baseline and differential.
DR   Genevisible; Q13153; HS.
DR   GO; GO:0005884; C:actin filament; IDA:UniProtKB.
DR   GO; GO:0030424; C:axon; ISS:UniProtKB.
DR   GO; GO:0005911; C:cell-cell junction; IDA:UniProtKB.
DR   GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR   GO; GO:0005925; C:focal adhesion; IEA:UniProtKB-SubCell.
DR   GO; GO:0014704; C:intercalated disc; ISS:UniProtKB.
DR   GO; GO:0071437; C:invadopodium; IDA:UniProtKB.
DR   GO; GO:0030027; C:lamellipodium; IEA:Ensembl.
DR   GO; GO:0031965; C:nuclear membrane; ISS:UniProtKB.
DR   GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IDA:HGNC-UCL.
DR   GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR   GO; GO:0001726; C:ruffle; IDA:UniProtKB.
DR   GO; GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0030018; C:Z disc; ISS:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0005518; F:collagen binding; IPI:UniProtKB.
DR   GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR   GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB.
DR   GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
DR   GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR   GO; GO:0031532; P:actin cytoskeleton reorganization; IDA:UniProtKB.
DR   GO; GO:0032147; P:activation of protein kinase activity; IBA:GO_Central.
DR   GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR   GO; GO:0048754; P:branching morphogenesis of an epithelial tube; IMP:UniProtKB.
DR   GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR   GO; GO:0032869; P:cellular response to insulin stimulus; IEA:Ensembl.
DR   GO; GO:0021549; P:cerebellum development; IEA:Ensembl.
DR   GO; GO:0006338; P:chromatin remodeling; IDA:UniProtKB.
DR   GO; GO:0048013; P:ephrin receptor signaling pathway; TAS:Reactome.
DR   GO; GO:0030010; P:establishment of cell polarity; IEA:Ensembl.
DR   GO; GO:0006887; P:exocytosis; IEA:UniProtKB-KW.
DR   GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome.
DR   GO; GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome.
DR   GO; GO:0048012; P:hepatocyte growth factor receptor signaling pathway; IMP:CAFA.
DR   GO; GO:0061052; P:negative regulation of cell growth involved in cardiac muscle cell development; IEA:Ensembl.
DR   GO; GO:0060244; P:negative regulation of cell proliferation involved in contact inhibition; IMP:UniProtKB.
DR   GO; GO:0048812; P:neuron projection morphogenesis; ISS:UniProtKB.
DR   GO; GO:0045773; P:positive regulation of axon extension; IEA:Ensembl.
DR   GO; GO:0030335; P:positive regulation of cell migration; IDA:UniProtKB.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:BHF-UCL.
DR   GO; GO:0010763; P:positive regulation of fibroblast migration; IEA:Ensembl.
DR   GO; GO:0046628; P:positive regulation of insulin receptor signaling pathway; IEA:Ensembl.
DR   GO; GO:0033148; P:positive regulation of intracellular estrogen receptor signaling pathway; IDA:UniProtKB.
DR   GO; GO:0043507; P:positive regulation of JUN kinase activity; IMP:UniProtKB.
DR   GO; GO:0031116; P:positive regulation of microtubule polymerization; IMP:CAFA.
DR   GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IDA:UniProtKB.
DR   GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:UniProtKB.
DR   GO; GO:0090314; P:positive regulation of protein targeting to membrane; IEA:Ensembl.
DR   GO; GO:0051496; P:positive regulation of stress fiber assembly; IMP:UniProtKB.
DR   GO; GO:1904754; P:positive regulation of vascular associated smooth muscle cell migration; IEA:Ensembl.
DR   GO; GO:1904707; P:positive regulation of vascular smooth muscle cell proliferation; IEA:Ensembl.
DR   GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR   GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR   GO; GO:0050770; P:regulation of axonogenesis; IBA:GO_Central.
DR   GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR   GO; GO:0023014; P:signal transduction by protein phosphorylation; IBA:GO_Central.
DR   GO; GO:0002223; P:stimulatory C-type lectin receptor signaling pathway; TAS:Reactome.
DR   GO; GO:0031295; P:T cell costimulation; TAS:Reactome.
DR   GO; GO:0050852; P:T cell receptor signaling pathway; TAS:Reactome.
DR   GO; GO:0042060; P:wound healing; IMP: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;
DR   PRODOM; Q13153.
DR   SWISS-2DPAGE; Q13153.
KW   3D-structure; Acetylation; Allosteric enzyme; Alternative splicing;
KW   Apoptosis; ATP-binding; Cell junction; Cell membrane; Cell projection;
KW   Chromosome; Cytoplasm; Disease mutation; Epilepsy; Exocytosis; Kinase;
KW   Membrane; Mental retardation; Nucleotide-binding; Nucleus; Phosphoprotein;
KW   Polymorphism; Reference proteome; Serine/threonine-protein kinase;
KW   Transferase.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000244|PubMed:22814378"
FT   CHAIN           2..545
FT                   /note="Serine/threonine-protein kinase PAK 1"
FT                   /id="PRO_0000086460"
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   NP_BIND         276..284
FT                   /note="ATP"
FT   NP_BIND         345..347
FT                   /note="ATP"
FT   REGION          70..140
FT                   /note="Autoregulatory region"
FT   REGION          75..105
FT                   /note="GTPase-binding"
FT   REGION          132..270
FT                   /note="Interaction with CRIPAK"
FT                   /evidence="ECO:0000269|PubMed:16278681"
FT   ACT_SITE        389
FT                   /note="Proton acceptor"
FT   BINDING         299
FT                   /note="ATP"
FT   MOD_RES         2
FT                   /note="N-acetylserine"
FT                   /evidence="ECO:0000244|PubMed:22814378"
FT   MOD_RES         21
FT                   /note="Phosphoserine; by PKB and autocatalysis"
FT                   /evidence="ECO:0000269|PubMed:14585966,
FT                   ECO:0000269|PubMed:17989089"
FT   MOD_RES         57
FT                   /note="Phosphoserine; by autocatalysis"
FT                   /evidence="ECO:0000269|PubMed:17989089"
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:0000244|PubMed:24275569"
FT   MOD_RES         131
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000269|PubMed:17989089"
FT   MOD_RES         142
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000269|PubMed:17989089"
FT   MOD_RES         144
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|PubMed:21406692"
FT   MOD_RES         149
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|PubMed:21406692"
FT   MOD_RES         153
FT                   /note="Phosphotyrosine; by JAK2"
FT                   /evidence="ECO:0000269|PubMed:17726028,
FT                   ECO:0000269|PubMed:17989089"
FT   MOD_RES         174
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|PubMed:21406692,
FT                   ECO:0000269|PubMed:17989089"
FT   MOD_RES         185
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000269|PubMed:17989089"
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:0000269|PubMed:17726028"
FT   MOD_RES         204
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|PubMed:19690332"
FT   MOD_RES         212
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000244|PubMed:16964243,
FT                   ECO:0000244|PubMed:19690332, ECO:0000269|PubMed:17989089,
FT                   ECO:0000269|PubMed:23260667"
FT   MOD_RES         219
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000244|PubMed:19690332"
FT   MOD_RES         220
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|PubMed:19690332"
FT   MOD_RES         223
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|PubMed:21406692"
FT   MOD_RES         225
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:O88643"
FT   MOD_RES         229
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:O88643"
FT   MOD_RES         230
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000244|PubMed:18669648,
FT                   ECO:0000244|PubMed:19690332, ECO:0000244|PubMed:21406692,
FT                   ECO:0000244|PubMed:23186163"
FT   MOD_RES         285
FT                   /note="Phosphotyrosine; by JAK2"
FT                   /evidence="ECO:0000269|PubMed:17726028,
FT                   ECO:0000269|PubMed:17989089"
FT   MOD_RES         423
FT                   /note="Phosphothreonine; by autocatalysis, BRSK2 and PDPK1"
FT                   /evidence="ECO:0000269|PubMed:10551809,
FT                   ECO:0000269|PubMed:10995762, ECO:0000269|PubMed:22153498,
FT                   ECO:0000269|PubMed:22669945"
FT   VAR_SEQ         518..545
FT                   /note="HQFLKIAKPLSSLTPLIAAAKEATKNNH -> VRKLRFQVFSNFSMIAASIP
FT                   EDCQAPLQPHSTDCCS (in isoform 2)"
FT                   /evidence="ECO:0000303|Ref.3"
FT                   /id="VSP_017507"
FT   VARIANT         131
FT                   /note="Y -> C (in IDDMSSD; gain of function; enhanced PAK1
FT                   kinase activity and significantly reduced
FT                   homodimerization)"
FT                   /evidence="ECO:0000269|PubMed:30290153"
FT                   /id="VAR_081554"
FT   VARIANT         429
FT                   /note="Y -> C (in IDDMSSD; gain-of-function; enhanced PAK1
FT                   kinase activity and significantly reduced
FT                   homodimerization)"
FT                   /evidence="ECO:0000269|PubMed:30290153"
FT                   /id="VAR_081555"
FT   VARIANT         515
FT                   /note="L -> V (in dbSNP:rs35345144)"
FT                   /id="VAR_051654"
FT   MUTAGEN         83
FT                   /note="H->L: Abolishes interaction with CDC42, leading to
FT                   strongly decreased activity; when associated with L-86."
FT                   /evidence="ECO:0000269|PubMed:10551809,
FT                   ECO:0000269|PubMed:9774440"
FT   MUTAGEN         86
FT                   /note="H->L: Abolishes interaction with CDC42, leading to
FT                   strongly decreased activity; when associated with L-83."
FT                   /evidence="ECO:0000269|PubMed:10551809,
FT                   ECO:0000269|PubMed:9774440"
FT   MUTAGEN         107
FT                   /note="L->F: Abolishes autoinhibition, leading to
FT                   constitutive kinase activity."
FT                   /evidence="ECO:0000269|PubMed:10551809"
FT   MUTAGEN         299
FT                   /note="K->R: Strongly decreases activity. Abolishes kinase
FT                   activity; when associated with N-389."
FT                   /evidence="ECO:0000269|PubMed:22153498"
FT   MUTAGEN         389
FT                   /note="D->N: Abolishes kinase activity; when associated
FT                   with R-299."
FT                   /evidence="ECO:0000269|PubMed:22153498"
FT   MUTAGEN         393
FT                   /note="D->A: Abolishes autophosphorylation at Thr-423."
FT   MUTAGEN         423
FT                   /note="T->A: Decreases CDC42-stimulated activity and
FT                   autophosphorylation."
FT                   /evidence="ECO:0000269|PubMed:10551809"
FT   MUTAGEN         423
FT                   /note="T->E: Constitutive kinase activity."
FT                   /evidence="ECO:0000269|PubMed:10551809"
FT   CONFLICT        26
FT                   /note="A -> V (in Ref. 2; AAA65441 and 3; AAC24716)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        237
FT                   /note="R -> L (in Ref. 1; AAC50590)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        379
FT                   /note="F -> S (in Ref. 1; AAC50590)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        503
FT                   /note="E -> D (in Ref. 2; AAA65441)"
FT                   /evidence="ECO:0000305"
FT   STRAND          79..87
FT                   /evidence="ECO:0000244|PDB:2QME"
FT   TURN            91..94
FT                   /evidence="ECO:0000244|PDB:2QME"
FT   STRAND          95..98
FT                   /evidence="ECO:0000244|PDB:1F3M"
FT   HELIX           101..108
FT                   /evidence="ECO:0000244|PDB:1F3M"
FT   HELIX           114..119
FT                   /evidence="ECO:0000244|PDB:1F3M"
FT   HELIX           121..135
FT                   /evidence="ECO:0000244|PDB:1F3M"
FT   STRAND          195..198
FT                   /evidence="ECO:0000244|PDB:1ZSG"
FT   STRAND          214..219
FT                   /evidence="ECO:0000244|PDB:3DVP"
FT   HELIX           250..260
FT                   /evidence="ECO:0000244|PDB:3FXZ"
FT   STRAND          261..264
FT                   /evidence="ECO:0000244|PDB:3FXZ"
FT   HELIX           266..268
FT                   /evidence="ECO:0000244|PDB:3FXZ"
FT   STRAND          270..272
FT                   /evidence="ECO:0000244|PDB:3Q4Z"
FT   STRAND          274..279
FT                   /evidence="ECO:0000244|PDB:3FXZ"
FT   STRAND          282..289
FT                   /evidence="ECO:0000244|PDB:3FXZ"
FT   TURN            290..292
FT                   /evidence="ECO:0000244|PDB:3FXZ"
FT   STRAND          295..302
FT                   /evidence="ECO:0000244|PDB:3FXZ"
FT   HELIX           303..305
FT                   /evidence="ECO:0000244|PDB:3FXZ"
FT   HELIX           309..321
FT                   /evidence="ECO:0000244|PDB:3FXZ"
FT   STRAND          330..336
FT                   /evidence="ECO:0000244|PDB:3FXZ"
FT   STRAND          339..345
FT                   /evidence="ECO:0000244|PDB:3FXZ"
FT   STRAND          349..351
FT                   /evidence="ECO:0000244|PDB:4ZJI"
FT   HELIX           352..358
FT                   /evidence="ECO:0000244|PDB:3FXZ"
FT   HELIX           363..382
FT                   /evidence="ECO:0000244|PDB:3FXZ"
FT   HELIX           392..394
FT                   /evidence="ECO:0000244|PDB:3FXZ"
FT   STRAND          395..397
FT                   /evidence="ECO:0000244|PDB:3FXZ"
FT   STRAND          403..405
FT                   /evidence="ECO:0000244|PDB:3FXZ"
FT   STRAND          408..410
FT                   /evidence="ECO:0000244|PDB:1F3M"
FT   STRAND          416..418
FT                   /evidence="ECO:0000244|PDB:3Q52"
FT   HELIX           428..430
FT                   /evidence="ECO:0000244|PDB:3FXZ"
FT   HELIX           433..437
FT                   /evidence="ECO:0000244|PDB:3FXZ"
FT   HELIX           444..459
FT                   /evidence="ECO:0000244|PDB:3FXZ"
FT   TURN            463..466
FT                   /evidence="ECO:0000244|PDB:3FXZ"
FT   HELIX           469..479
FT                   /evidence="ECO:0000244|PDB:3FXZ"
FT   HELIX           487..489
FT                   /evidence="ECO:0000244|PDB:3FXZ"
FT   HELIX           492..501
FT                   /evidence="ECO:0000244|PDB:3FXZ"
FT   TURN            506..508
FT                   /evidence="ECO:0000244|PDB:3FXZ"
FT   HELIX           512..515
FT                   /evidence="ECO:0000244|PDB:3FXZ"
FT   HELIX           519..523
FT                   /evidence="ECO:0000244|PDB:3FXZ"
FT   HELIX           527..530
FT                   /evidence="ECO:0000244|PDB:3FXZ"
FT   HELIX           531..540
FT                   /evidence="ECO:0000244|PDB:3FXZ"
SQ   SEQUENCE   545 AA;  60647 MW;  1A95CD5F2195CD7B CRC64;
     MSNNGLDIQD KPPAPPMRNT STMIGAGSKD AGTLNHGSKP LPPNPEEKKK KDRFYRSILP
     GDKTNKKKEK ERPEISLPSD FEHTIHVGFD AVTGEFTGMP EQWARLLQTS NITKSEQKKN
     PQAVLDVLEF YNSKKTSNSQ KYMSFTDKSA EDYNSSNALN VKAVSETPAV PPVSEDEDDD
     DDDATPPPVI APRPEHTKSV YTRSVIEPLP VTPTRDVATS PISPTENNTT PPDALTRNTE
     KQKKKPKMSD EEILEKLRSI VSVGDPKKKY TRFEKIGQGA SGTVYTAMDV ATGQEVAIKQ
     MNLQQQPKKE LIINEILVMR ENKNPNIVNY LDSYLVGDEL WVVMEYLAGG SLTDVVTETC
     MDEGQIAAVC RECLQALEFL HSNQVIHRDI KSDNILLGMD GSVKLTDFGF CAQITPEQSK
     RSTMVGTPYW MAPEVVTRKA YGPKVDIWSL GIMAIEMIEG EPPYLNENPL RALYLIATNG
     TPELQNPEKL SAIFRDFLNR CLEMDVEKRG SAKELLQHQF LKIAKPLSSL TPLIAAAKEA
     TKNNH
//

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