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 03-AUG-2022, entry version 233.
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 FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=11896197; DOI=10.1242/jcs.115.7.1497;
RA Manabe R., Kovalenko M., Webb D.J., Horwitz A.R.;
RT "GIT1 functions in a motile, multi-molecular signaling complex that
RT regulates protrusive activity and cell migration.";
RL J. Cell Sci. 115:1497-1510(2002).
RN [14]
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 [15]
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 [16]
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 [17]
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 [18]
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 [19]
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 [20]
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 [21]
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 [22]
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 [23]
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 [24]
RP CAUTION.
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 [25]
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 [26]
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 [27]
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 [28]
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 [29]
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 [30]
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 [31]
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 [32]
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 [33]
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 [34]
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 [35]
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 [36]
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 [37]
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 [38]
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 [39]
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 [40]
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 [41]
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 [42]
RP FUNCTION, INTERACTION WITH ARHGEF7; GAMMA-TUBULIN AND GIT1, AND SUBCELLULAR
RP LOCATION.
RX PubMed=27012601; DOI=10.1016/j.bbamcr.2016.03.016;
RA Cernohorska M., Sulimenko V., Hajkova Z., Sulimenko T., Sladkova V.,
RA Vinopal S., Draberova E., Draber P.;
RT "GIT1/betaPIX signaling proteins and PAK1 kinase regulate microtubule
RT nucleation.";
RL Biochim. Biophys. Acta 1863:1282-1297(2016).
RN [43]
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 [44]
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 [45]
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 [46]
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 [47]
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 [48]
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; ASP-389 AND
RP ASP-393, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, SUBUNIT, AND
RP PHOSPHORYLATION AT 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:11896197, PubMed:30290153). Can directly
CC phosphorylate BAD and protects cells against apoptosis. Activated by
CC interaction with CDC42 and RAC1. Functions as GTPase effector that
CC links the Rho-related GTPases CDC42 and RAC1 to the JNK MAP kinase
CC pathway. Phosphorylates and activates MAP2K1, and thereby mediates
CC activation of downstream MAP kinases. Involved in the reorganization of
CC the actin cytoskeleton, actin stress fibers and of focal adhesion
CC complexes. Phosphorylates the tubulin chaperone TBCB and thereby plays
CC a role in the regulation of microtubule biogenesis and organization of
CC the tubulin cytoskeleton. Plays a role in the regulation of insulin
CC secretion in response to elevated glucose levels. Part of a ternary
CC complex that contains PAK1, DVL1 and MUSK that is important for MUSK-
CC dependent regulation of AChR clustering during the formation of the
CC neuromuscular junction (NMJ). Activity is inhibited in cells undergoing
CC apoptosis, potentially due to binding of CDC2L1 and CDC2L2.
CC Phosphorylates MYL9/MLC2. Phosphorylates RAF1 at 'Ser-338' and 'Ser-
CC 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
CC (PubMed:25766321). In response to DNA damage, phosphorylates MORC2
CC which activates its ATPase activity and facilitates chromatin
CC remodeling (PubMed:23260667). In neurons, plays a crucial role in
CC regulating GABA(A) receptor synaptic stability and hence GABAergic
CC inhibitory synaptic transmission through its role in F-actin
CC stabilization (By similarity). In hippocampal neurons, necessary for
CC the formation of dendritic spines and excitatory synapses; this
CC function is dependent on kinase activity and may be exerted by the
CC regulation of actomyosin contractility through the phosphorylation of
CC myosin II regulatory light chain (MLC) (By similarity). Along with
CC GIT1, positively regulates microtubule nucleation during interphase
CC (PubMed:27012601). {ECO:0000250|UniProtKB:O88643,
CC ECO:0000250|UniProtKB:P35465, ECO:0000269|PubMed:10551809,
CC ECO:0000269|PubMed:11733498, ECO:0000269|PubMed:11896197,
CC ECO:0000269|PubMed:12624090, ECO:0000269|PubMed:12876277,
CC ECO:0000269|PubMed:14585966, ECO:0000269|PubMed:15611088,
CC ECO:0000269|PubMed:15831477, ECO:0000269|PubMed:15833848,
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:27012601, ECO:0000269|PubMed:30290153,
CC ECO:0000269|PubMed:8805275, ECO:0000269|PubMed:9032240,
CC ECO:0000269|PubMed:9395435, 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. Interacts with GIT1
CC (PubMed:27012601). Component of cytoplasmic complexes, which also
CC contains PXN, ARHGEF7 and GIT1. Interacts with NISCH (By similarity).
CC Interacts with DVL1; mediates the formation of a DVL1, MUSK and PAK1
CC ternary complex involved in AChR clustering (By similarity). Binds to
CC the caspase-cleaved p110 isoform of CDC2L1 and CDC2L2, p110C, but not
CC the full-length proteins (PubMed:12624090). Interacts with ARHGEF7
CC (PubMed:27012601, PubMed:16101281). Interacts tightly with GTP-bound
CC but not GDP-bound CDC42/P21 and RAC1 (By similarity). Probably found in
CC a ternary complex composed of DSCAM, PAK1 and RAC1. Interacts with
CC DSCAM (via cytoplasmic domain); the interaction is direct and enhanced
CC 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 BRSK2 (By similarity). Interacts with SNAI1
CC (PubMed:15833848). Interacts with CIB1 isoform 2 (PubMed:23503467).
CC Interacts with CIB1 (via N-terminal region); the interaction is direct,
CC promotes PAK1 activity and occurs in a calcium-dependent manner.
CC Interacts with INPP5K (PubMed:26940976). Interacts with gamma-tubulin
CC (PubMed:27012601). {ECO:0000250|UniProtKB:O88643,
CC ECO:0000250|UniProtKB:P35465, ECO:0000269|PubMed:10026169,
CC ECO:0000269|PubMed:10551809, ECO:0000269|PubMed:10995762,
CC ECO:0000269|PubMed:11733498, ECO:0000269|PubMed:11804587,
CC ECO:0000269|PubMed:12624090, ECO:0000269|PubMed:14585966,
CC ECO:0000269|PubMed:15169762, ECO:0000269|PubMed:15831477,
CC ECO:0000269|PubMed:15833848, ECO:0000269|PubMed:16061695,
CC ECO:0000269|PubMed:16101281, ECO:0000269|PubMed:16278681,
CC ECO:0000269|PubMed:18325335, ECO:0000269|PubMed:18716323,
CC ECO:0000269|PubMed:22153498, ECO:0000269|PubMed:22669945,
CC ECO:0000269|PubMed:23503467, ECO:0000269|PubMed:26940976,
CC ECO:0000269|PubMed:27012601, ECO:0000269|PubMed:30290153}.
CC -!- INTERACTION:
CC Q13153; P11117: ACP2; NbExp=3; IntAct=EBI-1307, EBI-2907070;
CC Q13153; P35611: ADD1; NbExp=3; IntAct=EBI-1307, EBI-2809187;
CC Q13153; Q15052: ARHGEF6; NbExp=4; IntAct=EBI-1307, EBI-1642523;
CC Q13153; Q14155: ARHGEF7; NbExp=12; IntAct=EBI-1307, EBI-717515;
CC Q13153; Q9H0W9-3: C11orf54; NbExp=3; IntAct=EBI-1307, EBI-12108466;
CC Q13153; P60953: CDC42; NbExp=12; IntAct=EBI-1307, EBI-81752;
CC Q13153; P21127: CDK11B; NbExp=4; IntAct=EBI-1307, EBI-1298;
CC Q13153; Q8N1N5: CRIPAK; NbExp=6; IntAct=EBI-1307, EBI-1205846;
CC Q13153; P63167: DYNLL1; NbExp=4; IntAct=EBI-1307, EBI-349105;
CC Q13153; Q6NZ36-4: FAAP20; NbExp=3; IntAct=EBI-1307, EBI-12013806;
CC Q13153; Q9Y2X7: GIT1; NbExp=5; IntAct=EBI-1307, EBI-466061;
CC Q13153; Q14161: GIT2; NbExp=3; IntAct=EBI-1307, EBI-1046878;
CC Q13153; Q13322-4: GRB10; NbExp=3; IntAct=EBI-1307, EBI-12353035;
CC Q13153; Q14145: KEAP1; NbExp=3; IntAct=EBI-1307, EBI-751001;
CC Q13153; Q9Y2M5: KLHL20; NbExp=3; IntAct=EBI-1307, EBI-714379;
CC Q13153; Q14847-2: LASP1; NbExp=3; IntAct=EBI-1307, EBI-9088686;
CC Q13153; P53667: LIMK1; NbExp=5; IntAct=EBI-1307, EBI-444403;
CC Q13153; Q15759: MAPK11; NbExp=3; IntAct=EBI-1307, EBI-298304;
CC Q13153; O43639: NCK2; NbExp=10; IntAct=EBI-1307, EBI-713635;
CC Q13153; Q9Y239: NOD1; NbExp=3; IntAct=EBI-1307, EBI-1051262;
CC Q13153; P32243-2: OTX2; NbExp=3; IntAct=EBI-1307, EBI-9087860;
CC Q13153; Q15365: PCBP1; NbExp=2; IntAct=EBI-1307, EBI-946095;
CC Q13153; Q8N490-3: PNKD; NbExp=3; IntAct=EBI-1307, EBI-25879276;
CC Q13153; P63000: RAC1; NbExp=25; IntAct=EBI-1307, EBI-413628;
CC Q13153; P63000-1: RAC1; NbExp=3; IntAct=EBI-1307, EBI-7212896;
CC Q13153; Q8WZ73-3: RFFL; NbExp=3; IntAct=EBI-1307, EBI-25839575;
CC Q13153; Q9H4E5: RHOJ; NbExp=3; IntAct=EBI-1307, EBI-6285694;
CC Q13153; Q92963: RIT1; NbExp=4; IntAct=EBI-1307, EBI-365845;
CC Q13153; Q9NTN9-3: SEMA4G; NbExp=3; IntAct=EBI-1307, EBI-9089805;
CC Q13153; Q96BD6: SPSB1; NbExp=3; IntAct=EBI-1307, EBI-2659201;
CC Q13153; O75558: STX11; NbExp=3; IntAct=EBI-1307, EBI-714135;
CC Q13153; O60506-4: SYNCRIP; NbExp=3; IntAct=EBI-1307, EBI-11123832;
CC Q13153; O15273: TCAP; NbExp=3; IntAct=EBI-1307, EBI-954089;
CC Q13153; Q8TDR4: TCP10L; NbExp=3; IntAct=EBI-1307, EBI-3923210;
CC Q13153; Q9BXU0: TEX12; NbExp=3; IntAct=EBI-1307, EBI-12090309;
CC Q13153; O60830: TIMM17B; NbExp=3; IntAct=EBI-1307, EBI-2372529;
CC Q13153; Q96A04: TSACC; NbExp=3; IntAct=EBI-1307, EBI-740411;
CC Q13153; Q9H892-2: TTC12; NbExp=3; IntAct=EBI-1307, EBI-10274410;
CC Q13153; Q96EF9: ZHX1-C8orf76; NbExp=3; IntAct=EBI-1307, EBI-25830993;
CC Q13153; Q8N0Y2-2: ZNF444; NbExp=3; IntAct=EBI-1307, EBI-12010736;
CC Q13153; P60766: Cdc42; Xeno; NbExp=3; IntAct=EBI-1307, EBI-81763;
CC Q13153; P63001: Rac1; Xeno; NbExp=3; IntAct=EBI-1307, EBI-413646;
CC Q13153; Q5PP90: US3(L); Xeno; NbExp=2; IntAct=EBI-1307, EBI-15780451;
CC Q13153-1; Q13153-1: PAK1; NbExp=2; IntAct=EBI-15628682, EBI-15628682;
CC Q13153-1; Q15365: PCBP1; NbExp=5; IntAct=EBI-15628682, EBI-946095;
CC Q13153-2; Q7L0Q8: RHOU; NbExp=2; IntAct=EBI-1019502, EBI-1638043;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11896197,
CC ECO:0000269|PubMed:23260667, ECO:0000269|PubMed:25766321}. Cell
CC junction, focal adhesion {ECO:0000269|PubMed:11896197,
CC ECO:0000269|PubMed:25766321}. Cell projection, lamellipodium
CC {ECO:0000269|PubMed:11896197}. 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}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000269|PubMed:27012601}.
CC Note=Colocalizes with RUFY3, F-actin and other core migration
CC components in invadopodia at the cell periphery (PubMed:25766321).
CC 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. Upon DNA damage, translocates to the nucleoplasm when
CC phosphorylated at Thr-212 where is co-recruited with MORC2 on damaged
CC chromatin (PubMed:23260667). Localization to the centrosome does not
CC depend upon the presence of gamma-tubulin (PubMed:27012601).
CC Localization of the active, but not inactive, protein to the adhesions
CC and edge of lamellipodia is mediated by interaction with GIT1
CC (PubMed:11896197). {ECO:0000250|UniProtKB:P35465,
CC ECO:0000269|PubMed:11896197, ECO:0000269|PubMed:23260667,
CC ECO:0000269|PubMed:25766321, ECO:0000269|PubMed:27012601}.
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 variants 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 -!- CAUTION: There are data describing interaction and regulation by the
CC product of CRIPAK, a putative single exon gene (PubMed:16278681).
CC However, considering all available data there is no sufficient
CC supporting evidence for the existence of such protein.
CC {ECO:0000269|PubMed:16278681, ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/PAK1ID41633ch11q13.html";
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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.
DR RefSeq; XP_011543383.1; XM_011545081.2.
DR RefSeq; XP_011543384.1; XM_011545082.2. [Q13153-2]
DR RefSeq; XP_011543385.1; XM_011545083.2.
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.
DR RefSeq; XP_016873337.1; XM_017017848.1.
DR RefSeq; XP_016873338.1; XM_017017849.1.
DR RefSeq; XP_016873339.1; XM_017017850.1.
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 AlphaFoldDB; Q13153; -.
DR BMRB; Q13153; -.
DR SMR; Q13153; -.
DR BioGRID; 111095; 183.
DR CORUM; Q13153; -.
DR DIP; DIP-31016N; -.
DR ELM; Q13153; -.
DR IntAct; Q13153; 172.
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 GlyGen; Q13153; 1 site.
DR iPTMnet; Q13153; -.
DR MetOSite; 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 Antibodypedia; 1132; 1444 antibodies from 50 providers.
DR DNASU; 5058; -.
DR Ensembl; ENST00000278568.8; ENSP00000278568.4; ENSG00000149269.10. [Q13153-2]
DR Ensembl; ENST00000356341.8; ENSP00000348696.4; ENSG00000149269.10. [Q13153-1]
DR GeneID; 5058; -.
DR KEGG; hsa:5058; -.
DR MANE-Select; ENST00000356341.8; ENSP00000348696.4; NM_002576.5; NP_002567.3.
DR UCSC; uc001oyg.5; human. [Q13153-1]
DR CTD; 5058; -.
DR DisGeNET; 5058; -.
DR GeneCards; PAK1; -.
DR HGNC; HGNC:8590; PAK1.
DR HPA; ENSG00000149269; Low tissue specificity.
DR MalaCards; PAK1; -.
DR MIM; 602590; gene.
DR MIM; 618158; phenotype.
DR neXtProt; NX_Q13153; -.
DR OpenTargets; ENSG00000149269; -.
DR PharmGKB; PA32917; -.
DR VEuPathDB; HostDB:ENSG00000149269; -.
DR eggNOG; KOG0578; Eukaryota.
DR GeneTree; ENSGT00950000182988; -.
DR InParanoid; Q13153; -.
DR OMA; IEISTPY; -.
DR OrthoDB; 757766at2759; -.
DR PhylomeDB; Q13153; -.
DR TreeFam; TF105351; -.
DR BRENDA; 2.7.11.1; 2681.
DR PathwayCommons; Q13153; -.
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 Reactome; R-HSA-9013148; CDC42 GTPase cycle.
DR Reactome; R-HSA-9013149; RAC1 GTPase cycle.
DR Reactome; R-HSA-9013404; RAC2 GTPase cycle.
DR Reactome; R-HSA-9013406; RHOQ GTPase cycle.
DR Reactome; R-HSA-9013407; RHOH GTPase cycle.
DR Reactome; R-HSA-9013409; RHOJ GTPase cycle.
DR Reactome; R-HSA-9013420; RHOU GTPase cycle.
DR Reactome; R-HSA-9013423; RAC3 GTPase cycle.
DR Reactome; R-HSA-9013424; RHOV GTPase cycle.
DR SignaLink; Q13153; -.
DR SIGNOR; Q13153; -.
DR BioGRID-ORCS; 5058; 21 hits in 1110 CRISPR screens.
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 middle temporal gyrus and 179 other tissues.
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:0030027; C:lamellipodium; IEA:UniProtKB-SubCell.
DR GO; GO:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell.
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:0043015; F:gamma-tubulin binding; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
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:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0048754; P:branching morphogenesis of an epithelial tube; IMP:UniProtKB.
DR GO; GO:0016477; P:cell migration; IMP:MGI.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0006338; P:chromatin remodeling; IDA:UniProtKB.
DR GO; GO:0048013; P:ephrin receptor signaling pathway; TAS:Reactome.
DR GO; GO:0006887; P:exocytosis; IEA:UniProtKB-KW.
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:0035556; P:intracellular signal transduction; IBA:GO_Central.
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:0016310; P:phosphorylation; IDA:UniProtKB.
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: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:0090063; P:positive regulation of microtubule nucleation; 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:0051496; P:positive regulation of stress fiber assembly; IMP:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; IBA:GO_Central.
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:0002223; P:stimulatory C-type lectin 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 IDEAL; IID00277; -.
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; Alternative splicing;
KW Apoptosis; ATP-binding; Cell junction; Cell membrane; Cell projection;
KW Chromosome; Cytoplasm; Cytoskeleton; Disease variant; Epilepsy; Exocytosis;
KW Intellectual disability; Kinase; Membrane; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|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 REGION 1..77
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 70..140
FT /note="Autoregulatory region"
FT REGION 75..105
FT /note="GTPase-binding"
FT REGION 159..198
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 211..251
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 42..77
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 216..236
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 237..251
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 389
FT /note="Proton acceptor"
FT BINDING 276..284
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 299
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 345..347
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|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:0007744|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:0007744|PubMed:21406692"
FT MOD_RES 149
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|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:0000269|PubMed:17989089,
FT ECO:0007744|PubMed:21406692"
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:0007744|PubMed:19690332"
FT MOD_RES 212
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:17989089,
FT ECO:0000269|PubMed:23260667, ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 219
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 220
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 223
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|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:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692,
FT ECO:0007744|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 homodimerization;
FT dbSNP:rs1565638316)"
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 homodimerization;
FT dbSNP:rs1565583382)"
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 /evidence="ECO:0000269|PubMed:22153498"
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:0007829|PDB:2QME"
FT TURN 91..94
FT /evidence="ECO:0007829|PDB:2QME"
FT STRAND 95..98
FT /evidence="ECO:0007829|PDB:1F3M"
FT HELIX 101..108
FT /evidence="ECO:0007829|PDB:1F3M"
FT HELIX 114..119
FT /evidence="ECO:0007829|PDB:1F3M"
FT HELIX 121..135
FT /evidence="ECO:0007829|PDB:1F3M"
FT STRAND 195..198
FT /evidence="ECO:0007829|PDB:1ZSG"
FT STRAND 214..219
FT /evidence="ECO:0007829|PDB:3DVP"
FT HELIX 250..260
FT /evidence="ECO:0007829|PDB:3FXZ"
FT STRAND 261..264
FT /evidence="ECO:0007829|PDB:3FXZ"
FT HELIX 266..268
FT /evidence="ECO:0007829|PDB:3FXZ"
FT STRAND 270..272
FT /evidence="ECO:0007829|PDB:3Q4Z"
FT STRAND 274..279
FT /evidence="ECO:0007829|PDB:3FXZ"
FT STRAND 282..289
FT /evidence="ECO:0007829|PDB:3FXZ"
FT TURN 290..292
FT /evidence="ECO:0007829|PDB:3FXZ"
FT STRAND 295..302
FT /evidence="ECO:0007829|PDB:3FXZ"
FT HELIX 303..305
FT /evidence="ECO:0007829|PDB:3FXZ"
FT HELIX 309..321
FT /evidence="ECO:0007829|PDB:3FXZ"
FT STRAND 330..336
FT /evidence="ECO:0007829|PDB:3FXZ"
FT STRAND 339..345
FT /evidence="ECO:0007829|PDB:3FXZ"
FT STRAND 349..351
FT /evidence="ECO:0007829|PDB:4ZJI"
FT HELIX 352..358
FT /evidence="ECO:0007829|PDB:3FXZ"
FT HELIX 363..382
FT /evidence="ECO:0007829|PDB:3FXZ"
FT HELIX 392..394
FT /evidence="ECO:0007829|PDB:3FXZ"
FT STRAND 395..397
FT /evidence="ECO:0007829|PDB:3FXZ"
FT STRAND 403..405
FT /evidence="ECO:0007829|PDB:3FXZ"
FT STRAND 408..410
FT /evidence="ECO:0007829|PDB:1F3M"
FT STRAND 416..418
FT /evidence="ECO:0007829|PDB:3Q52"
FT HELIX 428..430
FT /evidence="ECO:0007829|PDB:3FXZ"
FT HELIX 433..437
FT /evidence="ECO:0007829|PDB:3FXZ"
FT HELIX 444..459
FT /evidence="ECO:0007829|PDB:3FXZ"
FT TURN 463..466
FT /evidence="ECO:0007829|PDB:3FXZ"
FT HELIX 469..479
FT /evidence="ECO:0007829|PDB:3FXZ"
FT HELIX 487..489
FT /evidence="ECO:0007829|PDB:3FXZ"
FT HELIX 492..501
FT /evidence="ECO:0007829|PDB:3FXZ"
FT TURN 506..508
FT /evidence="ECO:0007829|PDB:3FXZ"
FT HELIX 512..515
FT /evidence="ECO:0007829|PDB:3FXZ"
FT HELIX 519..523
FT /evidence="ECO:0007829|PDB:3FXZ"
FT HELIX 527..530
FT /evidence="ECO:0007829|PDB:3FXZ"
FT HELIX 531..540
FT /evidence="ECO:0007829|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
