Full text data of PAK2
PAK2
[Confidence: low (only semi-automatic identification from reviews)]
Serine/threonine-protein kinase PAK 2; 2.7.11.1 (Gamma-PAK; PAK65; S6/H4 kinase; p21-activated kinase 2; PAK-2; p58; PAK-2p27; p27; PAK-2p34; p34; C-t-PAK2)
Serine/threonine-protein kinase PAK 2; 2.7.11.1 (Gamma-PAK; PAK65; S6/H4 kinase; p21-activated kinase 2; PAK-2; p58; PAK-2p27; p27; PAK-2p34; p34; C-t-PAK2)
UniProt
Q13177
ID PAK2_HUMAN Reviewed; 524 AA.
AC Q13177; Q13154; Q6ISC3;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 03-APR-2007, sequence version 3.
DT 22-JAN-2014, entry version 149.
DE RecName: Full=Serine/threonine-protein kinase PAK 2;
DE EC=2.7.11.1;
DE AltName: Full=Gamma-PAK;
DE AltName: Full=PAK65;
DE AltName: Full=S6/H4 kinase;
DE AltName: Full=p21-activated kinase 2;
DE Short=PAK-2;
DE AltName: Full=p58;
DE Contains:
DE RecName: Full=PAK-2p27;
DE Short=p27;
DE Contains:
DE RecName: Full=PAK-2p34;
DE Short=p34;
DE AltName: Full=C-t-PAK2;
GN Name=PAK2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Sells M., Knause U.J., Bagrodia S., Ambrose D., Bokoch G.M.,
RA Chernoff J.;
RL Submitted (APR-1995) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 32-524, AND PROTEIN SEQUENCE OF 401-417.
RC TISSUE=Placenta;
RX PubMed=7744004;
RA Martin G.A., Bollag G., McCormick F., Abo A.;
RT "A novel serine kinase activated by rac1/CDC42Hs-dependent
RT autophosphorylation is related to PAK65 and STE20.";
RL EMBO J. 14:1970-1978(1995).
RN [4]
RP ERRATUM.
RX PubMed=7556080;
RA Martin G.A., Bollag G., McCormick F., Abo A.;
RL EMBO J. 14:4385-4385(1995).
RN [5]
RP AUTOPHOSPHORYLATION.
RX PubMed=7673144; DOI=10.1074/jbc.270.36.21121;
RA Benner G.E., Dennis P.B., Masaracchia R.A.;
RT "Activation of an S6/H4 kinase (PAK 65) from human placenta by
RT intramolecular and intermolecular autophosphorylation.";
RL J. Biol. Chem. 270:21121-21128(1995).
RN [6]
RP CASPASE-3 CLEAVAGE AT ASP-512, FUNCTION, AND MUTAGENESIS OF ASP-212.
RX PubMed=9171063; DOI=10.1126/science.276.5318.1571;
RA Rudel T., Bokoch G.M.;
RT "Membrane and morphological changes in apoptotic cells regulated by
RT caspase-mediated activation of PAK2.";
RL Science 276:1571-1574(1997).
RN [7]
RP CASPASE-3 CLEAVAGE AT ASP-512, AUTOPHOSPHORYLATION, AND MUTAGENESIS OF
RP LYS-278 AND THR-402.
RX PubMed=9786869; DOI=10.1074/jbc.273.44.28733;
RA Walter B.N., Huang Z., Jakobi R., Tuazon P.T., Alnemri E.S.,
RA Litwack G., Traugh J.A.;
RT "Cleavage and activation of p21-activated protein kinase gamma-PAK by
RT CPP32 (caspase 3). Effects of autophosphorylation on activity.";
RL J. Biol. Chem. 273:28733-28739(1998).
RN [8]
RP INTERACTION WITH HIV-1 NEF.
RX PubMed=11070003; DOI=10.1128/JVI.74.23.11081-11087.2000;
RA Arora V.K., Molina R.P., Foster J.L., Blakemore J.L., Chernoff J.,
RA Fredericksen B.L., Garcia J.V.;
RT "Lentivirus Nef specifically activates Pak2.";
RL J. Virol. 74:11081-11087(2000).
RN [9]
RP FUNCTION (PAK-2P34), UBIQUITINATION, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF 239-ILE--GLY-243 AND 246-LYS--LYS-248.
RX PubMed=12853446; DOI=10.1074/jbc.M306494200;
RA Jakobi R., McCarthy C.C., Koeppel M.A., Stringer D.K.;
RT "Caspase-activated PAK-2 is regulated by subcellular targeting and
RT proteasomal degradation.";
RL J. Biol. Chem. 278:38675-38685(2003).
RN [10]
RP FUNCTION IN PHOSPHORYLATION OF MKNK1.
RX PubMed=15234964; DOI=10.1074/jbc.M407337200;
RA Orton K.C., Ling J., Waskiewicz A.J., Cooper J.A., Merrick W.C.,
RA Korneeva N.L., Rhoads R.E., Sonenberg N., Traugh J.A.;
RT "Phosphorylation of Mnk1 by caspase-activated Pak2/gamma-PAK inhibits
RT phosphorylation and interaction of eIF4G with Mnk.";
RL J. Biol. Chem. 279:38649-38657(2004).
RN [11]
RP INTERACTION WITH ARHGAP10, AND SUBCELLULAR LOCATION.
RX PubMed=15471851; DOI=10.1074/jbc.M410530200;
RA Koeppel M.A., McCarthy C.C., Moertl E., Jakobi R.;
RT "Identification and characterization of PS-GAP as a novel regulator of
RT caspase-activated PAK-2.";
RL J. Biol. Chem. 279:53653-53664(2004).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [13]
RP INTERACTION WITH SH3MD4.
RX PubMed=16374509; DOI=10.1038/sj.embor.7400596;
RA Kaerkkaeinen S., Hiipakka M., Wang J.-H., Kleino I.,
RA Vaehae-Jaakkola M., Renkema G.H., Liss M., Wagner R., Saksela K.;
RT "Identification of preferred protein interactions by phage-display of
RT the human Src homology-3 proteome.";
RL EMBO Rep. 7:186-191(2006).
RN [14]
RP FUNCTION (PAK-2P34), MYRISTOYLATION AT GLY-213 (PAK-2P34), AND
RP SUBCELLULAR LOCATION.
RX PubMed=16617111; DOI=10.1073/pnas.0600824103;
RA Vilas G.L., Corvi M.M., Plummer G.J., Seime A.M., Lambkin G.R.,
RA Berthiaume L.G.;
RT "Posttranslational myristoylation of caspase-activated p21-activated
RT protein kinase 2 (PAK2) potentiates late apoptotic events.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:6542-6547(2006).
RN [15]
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.,
RA Etienne-Manneville S., 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 [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-58; SER-141 AND THR-169,
RP AND MASS SPECTROMETRY.
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 [18]
RP INTERACTION WITH ARHGEF7 AND GIT1.
RX PubMed=19273597; DOI=10.1128/MCB.01713-08;
RA Mitsushima M., Toyoshima F., Nishida E.;
RT "Dual role of Cdc42 in spindle orientation control of adherent
RT cells.";
RL Mol. Cell. Biol. 29:2816-2827(2009).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-141 AND SER-197, AND
RP MASS SPECTROMETRY.
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 [20]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-128, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [21]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=19923322; DOI=10.1091/mbc.E09-03-0232;
RA Hsu R.M., Tsai M.H., Hsieh Y.J., Lyu P.C., Yu J.S.;
RT "Identification of MYO18A as a novel interacting partner of the
RT PAK2/betaPIX/GIT1 complex and its potential function in modulating
RT epithelial cell migration.";
RL Mol. Biol. Cell 21:287-301(2010).
RN [22]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-2 AND SER-141, MASS SPECTROMETRY, AND CLEAVAGE
RP OF INITIATOR METHIONINE.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [23]
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.,
RA Buerckstuemmer T., 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 [24]
RP AUTOPHOSPHORYLATION.
RX PubMed=21098037; DOI=10.1074/jbc.M110.156505;
RA Wang J., Wu J.W., Wang Z.X.;
RT "Mechanistic studies of the autoactivation of PAK2: a two-step model
RT of cis initiation followed by trans amplification.";
RL J. Biol. Chem. 286:2689-2695(2011).
RN [25]
RP FUNCTION IN PHOSPHORYLATION OF MAPK4 AND MAPK6.
RX PubMed=21317288; DOI=10.1074/jbc.M110.181743;
RA De la Mota-Peynado A., Chernoff J., Beeser A.;
RT "Identification of the atypical MAPK Erk3 as a novel substrate for
RT p21-activated kinase (Pak) activity.";
RL J. Biol. Chem. 286:13603-13611(2011).
RN [26]
RP FUNCTION IN PHOSPHORYLATION OF JUN.
RX PubMed=21177766; DOI=10.1093/carcin/bgq271;
RA Li T., Zhang J., Zhu F., Wen W., Zykova T., Li X., Liu K., Peng C.,
RA Ma W., Shi G., Dong Z., Bode A.M., Dong Z.;
RT "P21-activated protein kinase (PAK2)-mediated c-Jun phosphorylation at
RT 5 threonine sites promotes cell transformation.";
RL Carcinogenesis 32:659-666(2011).
RN [27]
RP FUNCTION IN PHOSPHORYLATION OF HISTONE H4.
RX PubMed=21724829; DOI=10.1101/gad.2055511;
RA Kang B., Pu M., Hu G., Wen W., Dong Z., Zhao K., Stillman B.,
RA Zhang Z.;
RT "Phosphorylation of H4 Ser 47 promotes HIRA-mediated nucleosome
RT assembly.";
RL Genes Dev. 25:1359-1364(2011).
RN [28]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-2; SER-141 AND THR-169, AND MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [29]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND MASS SPECTROMETRY.
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.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [30]
RP X-RAY CRYSTALLOGRAPHY (2.86 ANGSTROMS) OF 121-136.
RX PubMed=21170023; DOI=10.1038/nature09593;
RA Selyunin A.S., Sutton S.E., Weigele B.A., Reddick L.E., Orchard R.C.,
RA Bresson S.M., Tomchick D.R., Alto N.M.;
RT "The assembly of a GTPase-kinase signalling complex by a bacterial
RT catalytic scaffold.";
RL Nature 469:107-111(2011).
CC -!- FUNCTION: Serine/threonine protein kinase that plays a role in a
CC variety of different signaling pathways including cytoskeleton
CC regulation, cell motility, cell cycle progression, apoptosis or
CC proliferation. Acts as downstream effector of the small GTPases
CC CDC42 and RAC1. Activation by the binding of active CDC42 and RAC1
CC results in a conformational change and a subsequent
CC autophosphorylation on several serine and/or threonine residues.
CC Full-length PAK2 stimulates cell survival and cell growth.
CC Phosphorylates MAPK4 and MAPK6 and activates the downstream target
CC MAPKAPK5, a regulator of F-actin polymerization and cell
CC migration. Phosphorylates JUN and plays an important role in EGF-
CC induced cell proliferation. Phosphorylates many other substrates
CC including histone H4 to promote assembly of H3.3 and H4 into
CC nucleosomes, BAD, ribosomal protein S6, or MBP. Additionally,
CC associates with ARHGEF7 and GIT1 to perform kinase-independent
CC functions such as spindle orientation control during mitosis. On
CC the other hand, apoptotic stimuli such as DNA damage lead to
CC caspase-mediated cleavage of PAK2, generating PAK-2p34, an active
CC p34 fragment that translocates to the nucleus and promotes
CC cellular apoptosis involving the JNK signaling pathway. Caspase-
CC activated PAK2 phosphorylates MKNK1 and reduces cellular
CC translation.
CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
CC -!- ENZYME REGULATION: Activated by binding small G proteins. Binding
CC of GTP-bound CDC42 or RAC1 to the autoregulatory region releases
CC monomers from the autoinhibited dimer, enables phosphorylation of
CC Thr-402 and allows the kinase domain to adopt an active structure
CC (By similarity). Following caspase cleavage, autophosphorylated
CC PAK-2p34 is constitutively active.
CC -!- SUBUNIT: Interacts tightly with GTP-bound but not GDP-bound
CC CDC42/p21 and RAC1. Interacts with SH3MD4. Interacts with and
CC activated by HIV-1 Nef. Interacts with SCRIB. Interacts with
CC ARHGEF7 and GIT1. PAK-2p34 interacts with ARHGAP10.
CC -!- INTERACTION:
CC Self; NbExp=3; IntAct=EBI-1045887, EBI-1045887;
CC Q15052:ARHGEF6; NbExp=2; IntAct=EBI-1045887, EBI-1642523;
CC Q14155:ARHGEF7; NbExp=4; IntAct=EBI-1045887, EBI-717515;
CC O55043:Arhgef7 (xeno); NbExp=8; IntAct=EBI-1045887, EBI-3649585;
CC P55210:CASP7; NbExp=6; IntAct=EBI-1045887, EBI-523958;
CC P62993:GRB2; NbExp=2; IntAct=EBI-1045887, EBI-401755;
CC P08631:HCK; NbExp=2; IntAct=EBI-1045887, EBI-346340;
CC P42858:HTT; NbExp=2; IntAct=EBI-1045887, EBI-466029;
CC P53667:LIMK1; NbExp=2; IntAct=EBI-1045887, EBI-444403;
CC P16333:NCK1; NbExp=2; IntAct=EBI-1045887, EBI-389883;
CC P63000:RAC1; NbExp=4; IntAct=EBI-1045887, EBI-413628;
CC P04049:RAF1; NbExp=2; IntAct=EBI-1045887, EBI-365996;
CC Q8TEJ3:SH3RF3; NbExp=2; IntAct=EBI-1045887, EBI-7975674;
CC Q9BX66:SORBS1; NbExp=2; IntAct=EBI-1045887, EBI-433642;
CC O94875:SORBS2; NbExp=2; IntAct=EBI-1045887, EBI-311323;
CC O60504:SORBS3; NbExp=3; IntAct=EBI-1045887, EBI-741237;
CC P12931:SRC; NbExp=2; IntAct=EBI-1045887, EBI-621482;
CC -!- SUBCELLULAR LOCATION: Serine/threonine-protein kinase PAK 2:
CC Cytoplasm. Note=MYO18A mediates the cellular distribution of the
CC PAK2-ARHGEF7-GIT1 complex to the inner surface of the cell
CC membrane.
CC -!- SUBCELLULAR LOCATION: PAK-2p34: Nucleus. Cytoplasm, perinuclear
CC region. Membrane; Lipid-anchor. Note=Interaction with ARHGAP10
CC probably changes PAK-2p34 location to cytoplasmic perinuclear
CC region. Myristoylation changes PAK-2p34 location to the membrane.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. Higher levels seen in
CC skeletal muscle, ovary, thymus and spleen.
CC -!- PTM: Full length PAK2 is autophosphorylated when activated by
CC CDC42/p21. Following cleavage, both peptides, PAK-2p27 and PAK-
CC 2p34, become highly autophosphorylated, with PAK-2p27 being
CC phosphorylated on serine and PAK-2p34 on threonine residues,
CC respectively. Autophosphorylation of PAK-2p27 can occur in the
CC absence of any effectors and is dependent on phosphorylation of
CC Thr-402, because PAK-2p27 is acting as an exogenous substrate.
CC -!- PTM: During apoptosis proteolytically cleaved by caspase-3 or
CC caspase-3-like proteases to yield active PAK-2p34.
CC -!- PTM: Ubiquitinated, leading to its proteasomal degradation.
CC -!- PTM: PAK-2p34 is myristoylated.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. STE20 subfamily.
CC -!- SIMILARITY: Contains 1 CRIB domain.
CC -!- SIMILARITY: Contains 1 protein kinase domain.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/PAK2ID41634ch3q29.html";
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DR EMBL; U24153; AAA65442.1; -; mRNA.
DR EMBL; BC069613; AAH69613.1; -; mRNA.
DR EMBL; U25975; AAA75468.1; -; mRNA.
DR PIR; S58682; S58682.
DR RefSeq; NP_002568.2; NM_002577.4.
DR UniGene; Hs.518530; -.
DR PDB; 3PCS; X-ray; 2.86 A; E/F/G/H=121-136.
DR PDBsum; 3PCS; -.
DR ProteinModelPortal; Q13177; -.
DR SMR; Q13177; 69-143, 228-519.
DR DIP; DIP-38249N; -.
DR IntAct; Q13177; 31.
DR MINT; MINT-235655; -.
DR STRING; 9606.ENSP00000314067; -.
DR BindingDB; Q13177; -.
DR ChEMBL; CHEMBL4487; -.
DR GuidetoPHARMACOLOGY; 2134; -.
DR PhosphoSite; Q13177; -.
DR DMDM; 143811432; -.
DR OGP; Q13177; -.
DR PaxDb; Q13177; -.
DR PRIDE; Q13177; -.
DR DNASU; 5062; -.
DR Ensembl; ENST00000327134; ENSP00000314067; ENSG00000180370.
DR GeneID; 5062; -.
DR KEGG; hsa:5062; -.
DR UCSC; uc003fwy.4; human.
DR CTD; 5062; -.
DR GeneCards; GC03P196466; -.
DR H-InvDB; HIX0030815; -.
DR HGNC; HGNC:8591; PAK2.
DR HPA; CAB007794; -.
DR MIM; 605022; gene.
DR neXtProt; NX_Q13177; -.
DR PharmGKB; PA32918; -.
DR eggNOG; COG0515; -.
DR HOGENOM; HOG000234202; -.
DR HOVERGEN; HBG108518; -.
DR InParanoid; Q13177; -.
DR KO; K04410; -.
DR OMA; FSGAEKG; -.
DR PhylomeDB; Q13177; -.
DR BRENDA; 2.7.11.1; 2681.
DR Reactome; REACT_111045; Developmental Biology.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_578; Apoptosis.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; Q13177; -.
DR ChiTaRS; PAK2; human.
DR EvolutionaryTrace; Q13177; -.
DR GeneWiki; PAK2; -.
DR GenomeRNAi; 5062; -.
DR NextBio; 19496; -.
DR PMAP-CutDB; Q13177; -.
DR PRO; PR:Q13177; -.
DR ArrayExpress; Q13177; -.
DR Bgee; Q13177; -.
DR CleanEx; HS_PAK2; -.
DR Genevestigator; Q13177; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:BHF-UCL.
DR GO; GO:0030296; F:protein tyrosine kinase activator activity; IDA:BHF-UCL.
DR GO; GO:0007411; P:axon guidance; TAS:Reactome.
DR GO; GO:0006921; P:cellular component disassembly involved in execution phase of apoptosis; TAS:Reactome.
DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:2001271; P:negative regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis; IDA:UniProtKB.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; TAS:ProtInc.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:BHF-UCL.
DR GO; GO:2001238; P:positive regulation of extrinsic apoptotic signaling pathway; IMP:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:MGI.
DR GO; GO:0050690; P:regulation of defense response to virus by virus; TAS:Reactome.
DR GO; GO:0040008; P:regulation of growth; IEA:UniProtKB-KW.
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:0016032; P:viral process; TAS:Reactome.
DR Gene3D; 3.90.810.10; -; 1.
DR InterPro; IPR000095; CRIB_dom.
DR InterPro; IPR011009; Kinase-like_dom.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR002290; Ser/Thr_dual-sp_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00786; PBD; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00285; PBD; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50108; CRIB; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Allosteric enzyme; Apoptosis; ATP-binding;
KW Complete proteome; Cytoplasm; Direct protein sequencing;
KW Growth regulation; Host-virus interaction; Kinase; Lipoprotein;
KW Membrane; Myristate; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase;
KW Ubl conjugation.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 524 Serine/threonine-protein kinase PAK 2.
FT /FTId=PRO_0000086465.
FT CHAIN 2 212 PAK-2p27.
FT /FTId=PRO_0000304922.
FT CHAIN 213 524 PAK-2p34.
FT /FTId=PRO_0000304923.
FT DOMAIN 74 87 CRIB.
FT DOMAIN 249 499 Protein kinase.
FT NP_BIND 255 263 ATP (By similarity).
FT REGION 69 137 Autoregulatory region (By similarity).
FT REGION 69 112 GTPase-binding (By similarity).
FT MOTIF 245 251 Nuclear localization signal.
FT ACT_SITE 367 367 Proton acceptor (By similarity).
FT BINDING 278 278 ATP (By similarity).
FT SITE 212 213 Cleavage; by caspase-3 or caspase-3-like
FT proteases.
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 2 2 Phosphoserine.
FT MOD_RES 58 58 Phosphoserine.
FT MOD_RES 128 128 N6-acetyllysine.
FT MOD_RES 141 141 Phosphoserine.
FT MOD_RES 169 169 Phosphothreonine.
FT MOD_RES 197 197 Phosphoserine.
FT MOD_RES 402 402 Phosphothreonine; by autocatalysis
FT (Probable).
FT LIPID 213 213 N-myristoyl glycine; in form PAK-2p34.
FT MUTAGEN 212 212 D->N: Inhibits caspase-mediated cleavage.
FT MUTAGEN 213 213 G->A: Abolishes myristoylation of PAK-
FT 2p34 and membrane location.
FT MUTAGEN 239 243 IVSIG->REGRS: Abolishes nuclear export.
FT MUTAGEN 246 248 KKK->MHE: Greatly inhibits nuclear
FT localization.
FT MUTAGEN 278 278 K->R: Abolishes kinase activity and
FT autophosphorylation.
FT MUTAGEN 402 402 T->A: Abolishes kinase activity and
FT greatly inhibits autophosphorylation of
FT PAK-2p27 and PAK-2p34.
FT CONFLICT 90 90 A -> T (in Ref. 3; AAA75468).
FT CONFLICT 150 150 F -> L (in Ref. 1; AAA65442).
FT CONFLICT 225 225 T -> P (in Ref. 1; AAA65442).
FT CONFLICT 258 258 G -> R (in Ref. 2; AAH69613).
FT CONFLICT 329 329 G -> R (in Ref. 3; AAA75468).
FT CONFLICT 338 338 T -> TA (in Ref. 1; AAA65442).
FT HELIX 123 126
SQ SEQUENCE 524 AA; 58043 MW; 00A7CD15F93D4180 CRC64;
MSDNGELEDK PPAPPVRMSS TIFSTGGKDP LSANHSLKPL PSVPEEKKPR HKIISIFSGT
EKGSKKKEKE RPEISPPSDF EHTIHVGFDA VTGEFTGMPE QWARLLQTSN ITKLEQKKNP
QAVLDVLKFY DSNTVKQKYL SFTPPEKDGF PSGTPALNAK GTEAPAVVTE EEDDDEETAP
PVIAPRPDHT KSIYTRSVID PVPAPVGDSH VDGAAKSLDK QKKKTKMTDE EIMEKLRTIV
SIGDPKKKYT RYEKIGQGAS GTVFTATDVA LGQEVAIKQI NLQKQPKKEL IINEILVMKE
LKNPNIVNFL DSYLVGDELF VVMEYLAGGS LTDVVTETCM DEAQIAAVCR ECLQALEFLH
ANQVIHRDIK SDNVLLGMEG SVKLTDFGFC AQITPEQSKR STMVGTPYWM APEVVTRKAY
GPKVDIWSLG IMAIEMVEGE PPYLNENPLR ALYLIATNGT PELQNPEKLS PIFRDFLNRC
LEMDVEKRGS AKELLQHPFL KLAKPLSSLT PLIMAAKEAM KSNR
//
ID PAK2_HUMAN Reviewed; 524 AA.
AC Q13177; Q13154; Q6ISC3;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 03-APR-2007, sequence version 3.
DT 22-JAN-2014, entry version 149.
DE RecName: Full=Serine/threonine-protein kinase PAK 2;
DE EC=2.7.11.1;
DE AltName: Full=Gamma-PAK;
DE AltName: Full=PAK65;
DE AltName: Full=S6/H4 kinase;
DE AltName: Full=p21-activated kinase 2;
DE Short=PAK-2;
DE AltName: Full=p58;
DE Contains:
DE RecName: Full=PAK-2p27;
DE Short=p27;
DE Contains:
DE RecName: Full=PAK-2p34;
DE Short=p34;
DE AltName: Full=C-t-PAK2;
GN Name=PAK2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Sells M., Knause U.J., Bagrodia S., Ambrose D., Bokoch G.M.,
RA Chernoff J.;
RL Submitted (APR-1995) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 32-524, AND PROTEIN SEQUENCE OF 401-417.
RC TISSUE=Placenta;
RX PubMed=7744004;
RA Martin G.A., Bollag G., McCormick F., Abo A.;
RT "A novel serine kinase activated by rac1/CDC42Hs-dependent
RT autophosphorylation is related to PAK65 and STE20.";
RL EMBO J. 14:1970-1978(1995).
RN [4]
RP ERRATUM.
RX PubMed=7556080;
RA Martin G.A., Bollag G., McCormick F., Abo A.;
RL EMBO J. 14:4385-4385(1995).
RN [5]
RP AUTOPHOSPHORYLATION.
RX PubMed=7673144; DOI=10.1074/jbc.270.36.21121;
RA Benner G.E., Dennis P.B., Masaracchia R.A.;
RT "Activation of an S6/H4 kinase (PAK 65) from human placenta by
RT intramolecular and intermolecular autophosphorylation.";
RL J. Biol. Chem. 270:21121-21128(1995).
RN [6]
RP CASPASE-3 CLEAVAGE AT ASP-512, FUNCTION, AND MUTAGENESIS OF ASP-212.
RX PubMed=9171063; DOI=10.1126/science.276.5318.1571;
RA Rudel T., Bokoch G.M.;
RT "Membrane and morphological changes in apoptotic cells regulated by
RT caspase-mediated activation of PAK2.";
RL Science 276:1571-1574(1997).
RN [7]
RP CASPASE-3 CLEAVAGE AT ASP-512, AUTOPHOSPHORYLATION, AND MUTAGENESIS OF
RP LYS-278 AND THR-402.
RX PubMed=9786869; DOI=10.1074/jbc.273.44.28733;
RA Walter B.N., Huang Z., Jakobi R., Tuazon P.T., Alnemri E.S.,
RA Litwack G., Traugh J.A.;
RT "Cleavage and activation of p21-activated protein kinase gamma-PAK by
RT CPP32 (caspase 3). Effects of autophosphorylation on activity.";
RL J. Biol. Chem. 273:28733-28739(1998).
RN [8]
RP INTERACTION WITH HIV-1 NEF.
RX PubMed=11070003; DOI=10.1128/JVI.74.23.11081-11087.2000;
RA Arora V.K., Molina R.P., Foster J.L., Blakemore J.L., Chernoff J.,
RA Fredericksen B.L., Garcia J.V.;
RT "Lentivirus Nef specifically activates Pak2.";
RL J. Virol. 74:11081-11087(2000).
RN [9]
RP FUNCTION (PAK-2P34), UBIQUITINATION, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF 239-ILE--GLY-243 AND 246-LYS--LYS-248.
RX PubMed=12853446; DOI=10.1074/jbc.M306494200;
RA Jakobi R., McCarthy C.C., Koeppel M.A., Stringer D.K.;
RT "Caspase-activated PAK-2 is regulated by subcellular targeting and
RT proteasomal degradation.";
RL J. Biol. Chem. 278:38675-38685(2003).
RN [10]
RP FUNCTION IN PHOSPHORYLATION OF MKNK1.
RX PubMed=15234964; DOI=10.1074/jbc.M407337200;
RA Orton K.C., Ling J., Waskiewicz A.J., Cooper J.A., Merrick W.C.,
RA Korneeva N.L., Rhoads R.E., Sonenberg N., Traugh J.A.;
RT "Phosphorylation of Mnk1 by caspase-activated Pak2/gamma-PAK inhibits
RT phosphorylation and interaction of eIF4G with Mnk.";
RL J. Biol. Chem. 279:38649-38657(2004).
RN [11]
RP INTERACTION WITH ARHGAP10, AND SUBCELLULAR LOCATION.
RX PubMed=15471851; DOI=10.1074/jbc.M410530200;
RA Koeppel M.A., McCarthy C.C., Moertl E., Jakobi R.;
RT "Identification and characterization of PS-GAP as a novel regulator of
RT caspase-activated PAK-2.";
RL J. Biol. Chem. 279:53653-53664(2004).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [13]
RP INTERACTION WITH SH3MD4.
RX PubMed=16374509; DOI=10.1038/sj.embor.7400596;
RA Kaerkkaeinen S., Hiipakka M., Wang J.-H., Kleino I.,
RA Vaehae-Jaakkola M., Renkema G.H., Liss M., Wagner R., Saksela K.;
RT "Identification of preferred protein interactions by phage-display of
RT the human Src homology-3 proteome.";
RL EMBO Rep. 7:186-191(2006).
RN [14]
RP FUNCTION (PAK-2P34), MYRISTOYLATION AT GLY-213 (PAK-2P34), AND
RP SUBCELLULAR LOCATION.
RX PubMed=16617111; DOI=10.1073/pnas.0600824103;
RA Vilas G.L., Corvi M.M., Plummer G.J., Seime A.M., Lambkin G.R.,
RA Berthiaume L.G.;
RT "Posttranslational myristoylation of caspase-activated p21-activated
RT protein kinase 2 (PAK2) potentiates late apoptotic events.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:6542-6547(2006).
RN [15]
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.,
RA Etienne-Manneville S., 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 [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-58; SER-141 AND THR-169,
RP AND MASS SPECTROMETRY.
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 [18]
RP INTERACTION WITH ARHGEF7 AND GIT1.
RX PubMed=19273597; DOI=10.1128/MCB.01713-08;
RA Mitsushima M., Toyoshima F., Nishida E.;
RT "Dual role of Cdc42 in spindle orientation control of adherent
RT cells.";
RL Mol. Cell. Biol. 29:2816-2827(2009).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-141 AND SER-197, AND
RP MASS SPECTROMETRY.
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 [20]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-128, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [21]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=19923322; DOI=10.1091/mbc.E09-03-0232;
RA Hsu R.M., Tsai M.H., Hsieh Y.J., Lyu P.C., Yu J.S.;
RT "Identification of MYO18A as a novel interacting partner of the
RT PAK2/betaPIX/GIT1 complex and its potential function in modulating
RT epithelial cell migration.";
RL Mol. Biol. Cell 21:287-301(2010).
RN [22]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-2 AND SER-141, MASS SPECTROMETRY, AND CLEAVAGE
RP OF INITIATOR METHIONINE.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [23]
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.,
RA Buerckstuemmer T., 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 [24]
RP AUTOPHOSPHORYLATION.
RX PubMed=21098037; DOI=10.1074/jbc.M110.156505;
RA Wang J., Wu J.W., Wang Z.X.;
RT "Mechanistic studies of the autoactivation of PAK2: a two-step model
RT of cis initiation followed by trans amplification.";
RL J. Biol. Chem. 286:2689-2695(2011).
RN [25]
RP FUNCTION IN PHOSPHORYLATION OF MAPK4 AND MAPK6.
RX PubMed=21317288; DOI=10.1074/jbc.M110.181743;
RA De la Mota-Peynado A., Chernoff J., Beeser A.;
RT "Identification of the atypical MAPK Erk3 as a novel substrate for
RT p21-activated kinase (Pak) activity.";
RL J. Biol. Chem. 286:13603-13611(2011).
RN [26]
RP FUNCTION IN PHOSPHORYLATION OF JUN.
RX PubMed=21177766; DOI=10.1093/carcin/bgq271;
RA Li T., Zhang J., Zhu F., Wen W., Zykova T., Li X., Liu K., Peng C.,
RA Ma W., Shi G., Dong Z., Bode A.M., Dong Z.;
RT "P21-activated protein kinase (PAK2)-mediated c-Jun phosphorylation at
RT 5 threonine sites promotes cell transformation.";
RL Carcinogenesis 32:659-666(2011).
RN [27]
RP FUNCTION IN PHOSPHORYLATION OF HISTONE H4.
RX PubMed=21724829; DOI=10.1101/gad.2055511;
RA Kang B., Pu M., Hu G., Wen W., Dong Z., Zhao K., Stillman B.,
RA Zhang Z.;
RT "Phosphorylation of H4 Ser 47 promotes HIRA-mediated nucleosome
RT assembly.";
RL Genes Dev. 25:1359-1364(2011).
RN [28]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-2; SER-141 AND THR-169, AND MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [29]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND MASS SPECTROMETRY.
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.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [30]
RP X-RAY CRYSTALLOGRAPHY (2.86 ANGSTROMS) OF 121-136.
RX PubMed=21170023; DOI=10.1038/nature09593;
RA Selyunin A.S., Sutton S.E., Weigele B.A., Reddick L.E., Orchard R.C.,
RA Bresson S.M., Tomchick D.R., Alto N.M.;
RT "The assembly of a GTPase-kinase signalling complex by a bacterial
RT catalytic scaffold.";
RL Nature 469:107-111(2011).
CC -!- FUNCTION: Serine/threonine protein kinase that plays a role in a
CC variety of different signaling pathways including cytoskeleton
CC regulation, cell motility, cell cycle progression, apoptosis or
CC proliferation. Acts as downstream effector of the small GTPases
CC CDC42 and RAC1. Activation by the binding of active CDC42 and RAC1
CC results in a conformational change and a subsequent
CC autophosphorylation on several serine and/or threonine residues.
CC Full-length PAK2 stimulates cell survival and cell growth.
CC Phosphorylates MAPK4 and MAPK6 and activates the downstream target
CC MAPKAPK5, a regulator of F-actin polymerization and cell
CC migration. Phosphorylates JUN and plays an important role in EGF-
CC induced cell proliferation. Phosphorylates many other substrates
CC including histone H4 to promote assembly of H3.3 and H4 into
CC nucleosomes, BAD, ribosomal protein S6, or MBP. Additionally,
CC associates with ARHGEF7 and GIT1 to perform kinase-independent
CC functions such as spindle orientation control during mitosis. On
CC the other hand, apoptotic stimuli such as DNA damage lead to
CC caspase-mediated cleavage of PAK2, generating PAK-2p34, an active
CC p34 fragment that translocates to the nucleus and promotes
CC cellular apoptosis involving the JNK signaling pathway. Caspase-
CC activated PAK2 phosphorylates MKNK1 and reduces cellular
CC translation.
CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
CC -!- ENZYME REGULATION: Activated by binding small G proteins. Binding
CC of GTP-bound CDC42 or RAC1 to the autoregulatory region releases
CC monomers from the autoinhibited dimer, enables phosphorylation of
CC Thr-402 and allows the kinase domain to adopt an active structure
CC (By similarity). Following caspase cleavage, autophosphorylated
CC PAK-2p34 is constitutively active.
CC -!- SUBUNIT: Interacts tightly with GTP-bound but not GDP-bound
CC CDC42/p21 and RAC1. Interacts with SH3MD4. Interacts with and
CC activated by HIV-1 Nef. Interacts with SCRIB. Interacts with
CC ARHGEF7 and GIT1. PAK-2p34 interacts with ARHGAP10.
CC -!- INTERACTION:
CC Self; NbExp=3; IntAct=EBI-1045887, EBI-1045887;
CC Q15052:ARHGEF6; NbExp=2; IntAct=EBI-1045887, EBI-1642523;
CC Q14155:ARHGEF7; NbExp=4; IntAct=EBI-1045887, EBI-717515;
CC O55043:Arhgef7 (xeno); NbExp=8; IntAct=EBI-1045887, EBI-3649585;
CC P55210:CASP7; NbExp=6; IntAct=EBI-1045887, EBI-523958;
CC P62993:GRB2; NbExp=2; IntAct=EBI-1045887, EBI-401755;
CC P08631:HCK; NbExp=2; IntAct=EBI-1045887, EBI-346340;
CC P42858:HTT; NbExp=2; IntAct=EBI-1045887, EBI-466029;
CC P53667:LIMK1; NbExp=2; IntAct=EBI-1045887, EBI-444403;
CC P16333:NCK1; NbExp=2; IntAct=EBI-1045887, EBI-389883;
CC P63000:RAC1; NbExp=4; IntAct=EBI-1045887, EBI-413628;
CC P04049:RAF1; NbExp=2; IntAct=EBI-1045887, EBI-365996;
CC Q8TEJ3:SH3RF3; NbExp=2; IntAct=EBI-1045887, EBI-7975674;
CC Q9BX66:SORBS1; NbExp=2; IntAct=EBI-1045887, EBI-433642;
CC O94875:SORBS2; NbExp=2; IntAct=EBI-1045887, EBI-311323;
CC O60504:SORBS3; NbExp=3; IntAct=EBI-1045887, EBI-741237;
CC P12931:SRC; NbExp=2; IntAct=EBI-1045887, EBI-621482;
CC -!- SUBCELLULAR LOCATION: Serine/threonine-protein kinase PAK 2:
CC Cytoplasm. Note=MYO18A mediates the cellular distribution of the
CC PAK2-ARHGEF7-GIT1 complex to the inner surface of the cell
CC membrane.
CC -!- SUBCELLULAR LOCATION: PAK-2p34: Nucleus. Cytoplasm, perinuclear
CC region. Membrane; Lipid-anchor. Note=Interaction with ARHGAP10
CC probably changes PAK-2p34 location to cytoplasmic perinuclear
CC region. Myristoylation changes PAK-2p34 location to the membrane.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. Higher levels seen in
CC skeletal muscle, ovary, thymus and spleen.
CC -!- PTM: Full length PAK2 is autophosphorylated when activated by
CC CDC42/p21. Following cleavage, both peptides, PAK-2p27 and PAK-
CC 2p34, become highly autophosphorylated, with PAK-2p27 being
CC phosphorylated on serine and PAK-2p34 on threonine residues,
CC respectively. Autophosphorylation of PAK-2p27 can occur in the
CC absence of any effectors and is dependent on phosphorylation of
CC Thr-402, because PAK-2p27 is acting as an exogenous substrate.
CC -!- PTM: During apoptosis proteolytically cleaved by caspase-3 or
CC caspase-3-like proteases to yield active PAK-2p34.
CC -!- PTM: Ubiquitinated, leading to its proteasomal degradation.
CC -!- PTM: PAK-2p34 is myristoylated.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. STE20 subfamily.
CC -!- SIMILARITY: Contains 1 CRIB domain.
CC -!- SIMILARITY: Contains 1 protein kinase domain.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/PAK2ID41634ch3q29.html";
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DR EMBL; U24153; AAA65442.1; -; mRNA.
DR EMBL; BC069613; AAH69613.1; -; mRNA.
DR EMBL; U25975; AAA75468.1; -; mRNA.
DR PIR; S58682; S58682.
DR RefSeq; NP_002568.2; NM_002577.4.
DR UniGene; Hs.518530; -.
DR PDB; 3PCS; X-ray; 2.86 A; E/F/G/H=121-136.
DR PDBsum; 3PCS; -.
DR ProteinModelPortal; Q13177; -.
DR SMR; Q13177; 69-143, 228-519.
DR DIP; DIP-38249N; -.
DR IntAct; Q13177; 31.
DR MINT; MINT-235655; -.
DR STRING; 9606.ENSP00000314067; -.
DR BindingDB; Q13177; -.
DR ChEMBL; CHEMBL4487; -.
DR GuidetoPHARMACOLOGY; 2134; -.
DR PhosphoSite; Q13177; -.
DR DMDM; 143811432; -.
DR OGP; Q13177; -.
DR PaxDb; Q13177; -.
DR PRIDE; Q13177; -.
DR DNASU; 5062; -.
DR Ensembl; ENST00000327134; ENSP00000314067; ENSG00000180370.
DR GeneID; 5062; -.
DR KEGG; hsa:5062; -.
DR UCSC; uc003fwy.4; human.
DR CTD; 5062; -.
DR GeneCards; GC03P196466; -.
DR H-InvDB; HIX0030815; -.
DR HGNC; HGNC:8591; PAK2.
DR HPA; CAB007794; -.
DR MIM; 605022; gene.
DR neXtProt; NX_Q13177; -.
DR PharmGKB; PA32918; -.
DR eggNOG; COG0515; -.
DR HOGENOM; HOG000234202; -.
DR HOVERGEN; HBG108518; -.
DR InParanoid; Q13177; -.
DR KO; K04410; -.
DR OMA; FSGAEKG; -.
DR PhylomeDB; Q13177; -.
DR BRENDA; 2.7.11.1; 2681.
DR Reactome; REACT_111045; Developmental Biology.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_578; Apoptosis.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; Q13177; -.
DR ChiTaRS; PAK2; human.
DR EvolutionaryTrace; Q13177; -.
DR GeneWiki; PAK2; -.
DR GenomeRNAi; 5062; -.
DR NextBio; 19496; -.
DR PMAP-CutDB; Q13177; -.
DR PRO; PR:Q13177; -.
DR ArrayExpress; Q13177; -.
DR Bgee; Q13177; -.
DR CleanEx; HS_PAK2; -.
DR Genevestigator; Q13177; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:BHF-UCL.
DR GO; GO:0030296; F:protein tyrosine kinase activator activity; IDA:BHF-UCL.
DR GO; GO:0007411; P:axon guidance; TAS:Reactome.
DR GO; GO:0006921; P:cellular component disassembly involved in execution phase of apoptosis; TAS:Reactome.
DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:2001271; P:negative regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis; IDA:UniProtKB.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; TAS:ProtInc.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:BHF-UCL.
DR GO; GO:2001238; P:positive regulation of extrinsic apoptotic signaling pathway; IMP:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:MGI.
DR GO; GO:0050690; P:regulation of defense response to virus by virus; TAS:Reactome.
DR GO; GO:0040008; P:regulation of growth; IEA:UniProtKB-KW.
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:0016032; P:viral process; TAS:Reactome.
DR Gene3D; 3.90.810.10; -; 1.
DR InterPro; IPR000095; CRIB_dom.
DR InterPro; IPR011009; Kinase-like_dom.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR002290; Ser/Thr_dual-sp_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00786; PBD; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00285; PBD; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50108; CRIB; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Allosteric enzyme; Apoptosis; ATP-binding;
KW Complete proteome; Cytoplasm; Direct protein sequencing;
KW Growth regulation; Host-virus interaction; Kinase; Lipoprotein;
KW Membrane; Myristate; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase;
KW Ubl conjugation.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 524 Serine/threonine-protein kinase PAK 2.
FT /FTId=PRO_0000086465.
FT CHAIN 2 212 PAK-2p27.
FT /FTId=PRO_0000304922.
FT CHAIN 213 524 PAK-2p34.
FT /FTId=PRO_0000304923.
FT DOMAIN 74 87 CRIB.
FT DOMAIN 249 499 Protein kinase.
FT NP_BIND 255 263 ATP (By similarity).
FT REGION 69 137 Autoregulatory region (By similarity).
FT REGION 69 112 GTPase-binding (By similarity).
FT MOTIF 245 251 Nuclear localization signal.
FT ACT_SITE 367 367 Proton acceptor (By similarity).
FT BINDING 278 278 ATP (By similarity).
FT SITE 212 213 Cleavage; by caspase-3 or caspase-3-like
FT proteases.
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 2 2 Phosphoserine.
FT MOD_RES 58 58 Phosphoserine.
FT MOD_RES 128 128 N6-acetyllysine.
FT MOD_RES 141 141 Phosphoserine.
FT MOD_RES 169 169 Phosphothreonine.
FT MOD_RES 197 197 Phosphoserine.
FT MOD_RES 402 402 Phosphothreonine; by autocatalysis
FT (Probable).
FT LIPID 213 213 N-myristoyl glycine; in form PAK-2p34.
FT MUTAGEN 212 212 D->N: Inhibits caspase-mediated cleavage.
FT MUTAGEN 213 213 G->A: Abolishes myristoylation of PAK-
FT 2p34 and membrane location.
FT MUTAGEN 239 243 IVSIG->REGRS: Abolishes nuclear export.
FT MUTAGEN 246 248 KKK->MHE: Greatly inhibits nuclear
FT localization.
FT MUTAGEN 278 278 K->R: Abolishes kinase activity and
FT autophosphorylation.
FT MUTAGEN 402 402 T->A: Abolishes kinase activity and
FT greatly inhibits autophosphorylation of
FT PAK-2p27 and PAK-2p34.
FT CONFLICT 90 90 A -> T (in Ref. 3; AAA75468).
FT CONFLICT 150 150 F -> L (in Ref. 1; AAA65442).
FT CONFLICT 225 225 T -> P (in Ref. 1; AAA65442).
FT CONFLICT 258 258 G -> R (in Ref. 2; AAH69613).
FT CONFLICT 329 329 G -> R (in Ref. 3; AAA75468).
FT CONFLICT 338 338 T -> TA (in Ref. 1; AAA65442).
FT HELIX 123 126
SQ SEQUENCE 524 AA; 58043 MW; 00A7CD15F93D4180 CRC64;
MSDNGELEDK PPAPPVRMSS TIFSTGGKDP LSANHSLKPL PSVPEEKKPR HKIISIFSGT
EKGSKKKEKE RPEISPPSDF EHTIHVGFDA VTGEFTGMPE QWARLLQTSN ITKLEQKKNP
QAVLDVLKFY DSNTVKQKYL SFTPPEKDGF PSGTPALNAK GTEAPAVVTE EEDDDEETAP
PVIAPRPDHT KSIYTRSVID PVPAPVGDSH VDGAAKSLDK QKKKTKMTDE EIMEKLRTIV
SIGDPKKKYT RYEKIGQGAS GTVFTATDVA LGQEVAIKQI NLQKQPKKEL IINEILVMKE
LKNPNIVNFL DSYLVGDELF VVMEYLAGGS LTDVVTETCM DEAQIAAVCR ECLQALEFLH
ANQVIHRDIK SDNVLLGMEG SVKLTDFGFC AQITPEQSKR STMVGTPYWM APEVVTRKAY
GPKVDIWSLG IMAIEMVEGE PPYLNENPLR ALYLIATNGT PELQNPEKLS PIFRDFLNRC
LEMDVEKRGS AKELLQHPFL KLAKPLSSLT PLIMAAKEAM KSNR
//
MIM
605022
*RECORD*
*FIELD* NO
605022
*FIELD* TI
*605022 p21 PROTEIN-ACTIVATED KINASE 2; PAK2
;;p21 CDC42/RAC1-ACTIVATED KINASE 1;;
read morep21-ACTIVATED KINASE, 65-KD; PAK65
*FIELD* TX
For background information on p21-activated kinases (PAKs), see PAK1
(602590).
CLONING
Using screening assays for GTPases in neutrophil cytosol lysates,
followed by peptide sequence analysis and PCR on a placenta cDNA
library, Martin et al. (1995) isolated a full-length cDNA encoding human
PAK2, which they called PAK65. The deduced PAK2 protein contains RAC
(RAC1; 602048)- and CDC42 (116952)-binding domains. PAK2 shares 73%
amino acid identity with rat Pak1 (602590), including more than 95%
identity within the kinase domain. PAK2 also shares homology with the
yeast Ste20 gene. Northern blot analysis revealed that PAK2 is
ubiquitously expressed, with highest levels detected in skeletal muscle,
ovary, thymus, and spleen. PAK2 transcripts of 7.5, 5, 4.4, and 3 kb
were detected in most tissues. The 7.5-kb transcript was predominant in
all tissues tested except muscle, where the 7.5- and 3-kb transcripts
were equally expressed. In brain, a 3.3-kb transcript was expressed.
Genomic Southern blot analysis suggested that the multiple PAK2 mRNAs
result from alternative splicing. Western blot analysis using a human
PAK2 antibody detected PAK proteins in heart, kidney, liver, and very
strongly in purified neutrophil PAK2.
GENE FUNCTION
Binding analysis by Martin et al. (1995) confirmed that PAK2 associates
with the p21 proteins CDC42 and RAC1, but not with RHOA (ARHA; 165390).
Functional analysis determined that CDC42 and RAC1 induce
autophosphorylation of PAK2, which stimulates sustained phosphorylation
of other substrates.
Knaus et al. (1995) biochemically purified PAK1 and PAK2 from
neutrophils. They showed that stimulation of neutrophils with the
chemoattractant FMLP stimulates kinase activity of PAK1 and PAK2.
PAK2 is unique among PAK family members in that it can be activated by
proteolytic cleavage to generate a constitutively active fragment,
PAK2p34. Activation of PAK2 by RAC or CDC42 stimulates cell survival,
whereas caspase-activated PAK2p34 induces a cell death response. Using
yeast 2-hybrid analysis, Koeppel et al. (2004) determined that PSGAP
(ARHGAP10; 609746) interacted specifically with PAK2p34, but not with
active or inactive full-length PAK2, in vitro and in vivo via a region
between the GAP and SH3 domains of PSGAP. The interaction with PSGAP
inhibited the protein kinase activity of PAK2p34 in vitro and changed
the localization of PAK2p24 from the nucleus to the perinuclear region.
Furthermore, PSGAP appeared to regulate the ability of PAK2p34 to induce
programmed cell death.
That the PAK2 and DLG1 (601014) genes, both of which map within the
microdeletion that defines the 3q29 microdeletion syndrome, are
autosomal homologs of 2 X-linked mental retardation genes, PAK3 (300142)
and DLG3 (300189), suggested to Willatt et al. (2005) the possibility of
their involvement in the phenotype.
MAPPING
Willatt et al. (2005) identified the PAK2 gene within a 1.5-Mb region on
chromosome 3q29 that defines the 3q29 microdeletion syndrome (609425).
*FIELD* RF
1. Knaus, U. G.; Morris, S.; Dong, H.-J.; Chernoff, J.; Bokoch, G.
M.: Regulation of human leukocyte p21-activated kinases through G
protein-coupled receptors. Science 269: 221-223, 1995.
2. Koeppel, M. A.; McCarthy, C. C.; Moertl, E.; Jakobi, R.: Identification
and characterization of PS-GAP as a novel regulator of caspase-activated
PAK-2. J. Biol. Chem. 279: 53653-53664, 2004.
3. Martin, G. A.; Bollag, G.; McCormick, F.; Abo, A.: A novel serine
kinase activated by rac1/CDC42Hs-dependent autophosphorylation is
related to PAK65 and STE20. EMBO J. 14: 1970-1978, 1995. Note: Erratum:
EMBO J. 14: 4385 only, 1995.
4. Willatt, L.; Cox, J.; Barber, J.; Cabanas, E. D.; Collins, A.;
Donnai, D.; FitzPatrick, D. R.; Maher, E.; Martin, H.; Parnau, J.;
Pindar, L.; Ramsay, J.; Shaw-Smith, C.; Sistermans, E. A.; Tettenborn,
M.; Trump, D.; de Vries, B. B. A.; Walker, K.; Raymond, F. L.: 3q29
microdeletion syndrome: clinical and molecular characterization of
a new syndrome. Am. J. Hum. Genet. 77: 154-160, 2005.
*FIELD* CN
Matthew B. Gross - updated: 11/28/2005
Victor A. McKusick - updated: 6/17/2005
*FIELD* CD
Paul J. Converse: 5/31/2000
*FIELD* ED
carol: 08/17/2012
mgross: 5/9/2011
mgross: 11/28/2005
alopez: 6/21/2005
terry: 6/17/2005
mgross: 5/31/2000
*RECORD*
*FIELD* NO
605022
*FIELD* TI
*605022 p21 PROTEIN-ACTIVATED KINASE 2; PAK2
;;p21 CDC42/RAC1-ACTIVATED KINASE 1;;
read morep21-ACTIVATED KINASE, 65-KD; PAK65
*FIELD* TX
For background information on p21-activated kinases (PAKs), see PAK1
(602590).
CLONING
Using screening assays for GTPases in neutrophil cytosol lysates,
followed by peptide sequence analysis and PCR on a placenta cDNA
library, Martin et al. (1995) isolated a full-length cDNA encoding human
PAK2, which they called PAK65. The deduced PAK2 protein contains RAC
(RAC1; 602048)- and CDC42 (116952)-binding domains. PAK2 shares 73%
amino acid identity with rat Pak1 (602590), including more than 95%
identity within the kinase domain. PAK2 also shares homology with the
yeast Ste20 gene. Northern blot analysis revealed that PAK2 is
ubiquitously expressed, with highest levels detected in skeletal muscle,
ovary, thymus, and spleen. PAK2 transcripts of 7.5, 5, 4.4, and 3 kb
were detected in most tissues. The 7.5-kb transcript was predominant in
all tissues tested except muscle, where the 7.5- and 3-kb transcripts
were equally expressed. In brain, a 3.3-kb transcript was expressed.
Genomic Southern blot analysis suggested that the multiple PAK2 mRNAs
result from alternative splicing. Western blot analysis using a human
PAK2 antibody detected PAK proteins in heart, kidney, liver, and very
strongly in purified neutrophil PAK2.
GENE FUNCTION
Binding analysis by Martin et al. (1995) confirmed that PAK2 associates
with the p21 proteins CDC42 and RAC1, but not with RHOA (ARHA; 165390).
Functional analysis determined that CDC42 and RAC1 induce
autophosphorylation of PAK2, which stimulates sustained phosphorylation
of other substrates.
Knaus et al. (1995) biochemically purified PAK1 and PAK2 from
neutrophils. They showed that stimulation of neutrophils with the
chemoattractant FMLP stimulates kinase activity of PAK1 and PAK2.
PAK2 is unique among PAK family members in that it can be activated by
proteolytic cleavage to generate a constitutively active fragment,
PAK2p34. Activation of PAK2 by RAC or CDC42 stimulates cell survival,
whereas caspase-activated PAK2p34 induces a cell death response. Using
yeast 2-hybrid analysis, Koeppel et al. (2004) determined that PSGAP
(ARHGAP10; 609746) interacted specifically with PAK2p34, but not with
active or inactive full-length PAK2, in vitro and in vivo via a region
between the GAP and SH3 domains of PSGAP. The interaction with PSGAP
inhibited the protein kinase activity of PAK2p34 in vitro and changed
the localization of PAK2p24 from the nucleus to the perinuclear region.
Furthermore, PSGAP appeared to regulate the ability of PAK2p34 to induce
programmed cell death.
That the PAK2 and DLG1 (601014) genes, both of which map within the
microdeletion that defines the 3q29 microdeletion syndrome, are
autosomal homologs of 2 X-linked mental retardation genes, PAK3 (300142)
and DLG3 (300189), suggested to Willatt et al. (2005) the possibility of
their involvement in the phenotype.
MAPPING
Willatt et al. (2005) identified the PAK2 gene within a 1.5-Mb region on
chromosome 3q29 that defines the 3q29 microdeletion syndrome (609425).
*FIELD* RF
1. Knaus, U. G.; Morris, S.; Dong, H.-J.; Chernoff, J.; Bokoch, G.
M.: Regulation of human leukocyte p21-activated kinases through G
protein-coupled receptors. Science 269: 221-223, 1995.
2. Koeppel, M. A.; McCarthy, C. C.; Moertl, E.; Jakobi, R.: Identification
and characterization of PS-GAP as a novel regulator of caspase-activated
PAK-2. J. Biol. Chem. 279: 53653-53664, 2004.
3. Martin, G. A.; Bollag, G.; McCormick, F.; Abo, A.: A novel serine
kinase activated by rac1/CDC42Hs-dependent autophosphorylation is
related to PAK65 and STE20. EMBO J. 14: 1970-1978, 1995. Note: Erratum:
EMBO J. 14: 4385 only, 1995.
4. Willatt, L.; Cox, J.; Barber, J.; Cabanas, E. D.; Collins, A.;
Donnai, D.; FitzPatrick, D. R.; Maher, E.; Martin, H.; Parnau, J.;
Pindar, L.; Ramsay, J.; Shaw-Smith, C.; Sistermans, E. A.; Tettenborn,
M.; Trump, D.; de Vries, B. B. A.; Walker, K.; Raymond, F. L.: 3q29
microdeletion syndrome: clinical and molecular characterization of
a new syndrome. Am. J. Hum. Genet. 77: 154-160, 2005.
*FIELD* CN
Matthew B. Gross - updated: 11/28/2005
Victor A. McKusick - updated: 6/17/2005
*FIELD* CD
Paul J. Converse: 5/31/2000
*FIELD* ED
carol: 08/17/2012
mgross: 5/9/2011
mgross: 11/28/2005
alopez: 6/21/2005
terry: 6/17/2005
mgross: 5/31/2000