ID PDPK1_HUMAN Reviewed; 556 AA. AC O15530; H0Y4Z0; Q59EH6; Q6FI20; Q8IV52; Q9BRD5; DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot. DT 01-JAN-1998, sequence version 1. DT 27-MAR-2024, entry version 243. DE RecName: Full=3-phosphoinositide-dependent protein kinase 1; DE Short=hPDK1; DE EC=2.7.11.1; GN Name=PDPK1; Synonyms=PDK1; 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 IN PHOSPHORYLATION OF RP PKB/AKT1. RX PubMed=9094314; DOI=10.1016/s0960-9822(06)00122-9; RA Alessi D.R., James S.R., Downes C.P., Holmes A.B., Gaffney P.R.J., RA Reese C.B., Cohen P.; RT "Characterization of a 3-phosphoinositide-dependent protein kinase which RT phosphorylates and activates protein kinase B alpha."; RL Curr. Biol. 7:261-269(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=9368760; DOI=10.1016/s0960-9822(06)00336-8; RA Alessi D.R., Deak M., Casamayor A., Caudwell F.B., Morrice N.A., RA Norman D.G., Gaffney P.R.J., Reese C.B., MacDougall C.N., Harbison D., RA Ashworth A., Bownes M.; RT "3-phosphoinositide-dependent protein kinase-1 (PDK1): structural and RT functional homology with the Drosophila DSTPK61 kinase."; RL Curr. Biol. 7:776-789(1997). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3). RC TISSUE=Myeloid; RX PubMed=9445477; DOI=10.1126/science.279.5351.710; RA Stephens L.R., Anderson K.E., Stokoe D., Erdjument-Bromage H., RA Painter G.F., Holmes A.B., Gaffney P.R.J., Reese C.B., McCormick F., RA Tempst P., Coadwell W.J., Hawkins P.T.; RT "Protein kinase B kinases that mediate phosphatidylinositol 3,4,5- RT trisphosphate-dependent activation of protein kinase B."; RL Science 279:710-714(1998). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5). RC TISSUE=Brain; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., RA Ohara O., Nagase T., Kikuno R.F.; RT "Homo sapiens protein coding cDNA."; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15616553; DOI=10.1038/nature03187; RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M., RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., RA Myers R.M., Rubin E.M., Pennacchio L.A.; RT "The sequence and analysis of duplication-rich human chromosome 16."; RL Nature 432:988-994(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 4). RC TISSUE=Brain, Kidney, and Uterus; 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 [8] RP PROTEIN SEQUENCE OF 60-75; 87-100; 184-199; 239-257 AND 284-293, RP PHOSPHORYLATION AT SER-241, AND IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Embryonic kidney; RA Bienvenut W.V., Waridel P., Quadroni M.; RL Submitted (MAR-2009) to UniProtKB. RN [9] RP MUTAGENESIS OF ARG-474, AND ALTERNATIVE SPLICING. RX PubMed=9637919; DOI=10.1016/s0960-9822(98)70274-x; RA Anderson K.E., Coadwell W.J., Stephens L.R., Hawkins P.T.; RT "Translocation of PDK-1 to the plasma membrane is important in allowing RT PDK-1 to activate protein kinase B."; RL Curr. Biol. 8:684-691(1998). RN [10] RP FUNCTION IN PHOSPHORYLATION OF PRKCZ. RX PubMed=9768361; DOI=10.1016/s0960-9822(98)70444-0; RA Chou M.M., Hou W., Johnson J., Graham L.K., Lee M.H., Chen C.S., RA Newton A.C., Schaffhausen B.S., Toker A.; RT "Regulation of protein kinase C zeta by PI 3-kinase and PDK-1."; RL Curr. Biol. 8:1069-1077(1998). RN [11] RP FUNCTION IN PHOSPHORYLATION OF PRKACA. RX PubMed=9707564; DOI=10.1073/pnas.95.17.9849; RA Cheng X., Ma Y., Moore M., Hemmings B.A., Taylor S.S.; RT "Phosphorylation and activation of cAMP-dependent protein kinase by RT phosphoinositide-dependent protein kinase."; RL Proc. Natl. Acad. Sci. U.S.A. 95:9849-9854(1998). RN [12] RP FUNCTION IN PHOSPHORYLATION OF RPS6KB1. RX PubMed=9445476; DOI=10.1126/science.279.5351.707; RA Pullen N., Dennis P.B., Andjelkovic M., Dufner A., Kozma S.C., RA Hemmings B.A., Thomas G.; RT "Phosphorylation and activation of p70s6k by PDK1."; RL Science 279:707-710(1998). RN [13] RP PHOSPHORYLATION AT SER-25; SER-241; SER-393; SER-396 AND SER-410, AND RP MUTAGENESIS OF SER-25; SER-241; SER-393; SER-396 AND SER-410. RX PubMed=10455013; DOI=10.1042/bj3420287; RA Casamayor A., Morrice N.A., Alessi D.R.; RT "Phosphorylation of Ser-241 is essential for the activity of 3- RT phosphoinositide-dependent protein kinase-1: identification of five sites RT of phosphorylation in vivo."; RL Biochem. J. 342:287-292(1999). RN [14] RP MUTAGENESIS OF ALA-277. RX PubMed=10364160; DOI=10.1101/gad.13.11.1438; RA Paradis S., Ailion M., Toker A., Thomas J.H., Ruvkun G.; RT "A PDK1 homolog is necessary and sufficient to transduce AGE-1 PI3 kinase RT signals that regulate diapause in Caenorhabditis elegans."; RL Genes Dev. 13:1438-1452(1999). RN [15] RP FUNCTION IN PHOSPHORYLATION OF RPS6KA3. RX PubMed=10480933; DOI=10.1074/jbc.274.38.27168; RA Jensen C.J., Buch M.-B., Krag T.O., Hemmings B.A., Gammeltoft S., RA Froedin M.; RT "90-kDa ribosomal S6 kinase is phosphorylated and activated by 3- RT phosphoinositide-dependent protein kinase-1."; RL J. Biol. Chem. 274:27168-27176(1999). RN [16] RP FUNCTION IN PHOSPHORYLATION OF PAK1, AND INTERACTION WITH PAK1. 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 [17] RP PHOSPHORYLATION AT TYR-9; SER-241; TYR-373 AND TYR-376, AND MUTAGENESIS OF RP TYR-9; TYR-373 AND TYR-376. RX PubMed=11481331; DOI=10.1074/jbc.m105916200; RA Park J., Hill M.M., Hess D., Brazil D.P., Hofsteenge J., Hemmings B.A.; RT "Identification of tyrosine phosphorylation sites on 3-phosphoinositide- RT dependent protein kinase-1 (PDK1) and their role in regulating kinase RT activity."; RL J. Biol. Chem. 276:37459-37471(2001). RN [18] RP ACTIVITY REGULATION, AND INTERACTION WITH YWHAH AND YWHAQ. RX PubMed=12177059; DOI=10.1074/jbc.m205141200; RA Sato S., Fujita N., Tsuruo T.; RT "Regulation of kinase activity of 3-phosphoinositide-dependent protein RT kinase-1 by binding to 14-3-3."; RL J. Biol. Chem. 277:39360-39367(2002). RN [19] RP FUNCTION IN PHOSPHORYLATION OF PKB/AKT1. RX PubMed=12167717; DOI=10.1128/mcb.22.17.6247-6260.2002; RA Scheid M.P., Marignani P.A., Woodgett J.R.; RT "Multiple phosphoinositide 3-kinase-dependent steps in activation of RT protein kinase B."; RL Mol. Cell. Biol. 22:6247-6260(2002). RN [20] RP FUNCTION, PHOSPHORYLATION AT TYR-9; TYR-373 AND TYR-376 BY SRC, INTERACTION RP WITH PTK2B, AND SUBCELLULAR LOCATION. RX PubMed=14585963; DOI=10.1128/mcb.23.22.8019-8029.2003; RA Taniyama Y., Weber D.S., Rocic P., Hilenski L., Akers M.L., Park J., RA Hemmings B.A., Alexander R.W., Griendling K.K.; RT "Pyk2- and Src-dependent tyrosine phosphorylation of PDK1 regulates focal RT adhesions."; RL Mol. Cell. Biol. 23:8019-8029(2003). RN [21] RP FUNCTION IN PHOSPHORYLATION OF SGK3, AND INTERACTION WITH SGK3. RX PubMed=14604990; DOI=10.1074/jbc.m309653200; RA Nilsen T., Slagsvold T., Skjerpen C.S., Brech A., Stenmark H., Olsnes S.; RT "Peroxisomal targeting as a tool for assaying protein-protein interactions RT in the living cell: cytokine-independent survival kinase (CISK) binds PDK-1 RT in vivo in a phosphorylation-dependent manner."; RL J. Biol. Chem. 279:4794-4801(2004). RN [22] RP SUBCELLULAR LOCATION, AND INTERACTION WITH GRB14. RX PubMed=15210700; DOI=10.1074/jbc.m405340200; RA King C.C., Newton A.C.; RT "The adaptor protein Grb14 regulates the localization of 3- RT phosphoinositide-dependent kinase-1."; RL J. Biol. Chem. 279:37518-37527(2004). RN [23] RP FUNCTION IN PHOSPHORYLATION OF AKT1, AND INTERACTION WITH PKN2. RX PubMed=10226025; DOI=10.1016/s0960-9822(99)80186-9; RA Balendran A., Casamayor A., Deak M., Paterson A., Gaffney P., Currie R., RA Downes C.P., Alessi D.R.; RT "PDK1 acquires PDK2 activity in the presence of a synthetic peptide derived RT from the carboxyl terminus of PRK2."; RL Curr. Biol. 9:393-404(1999). RN [24] RP REVIEW ON FUNCTION. RX PubMed=15209375; DOI=10.1016/j.semcdb.2003.12.022; RA Mora A., Komander D., van Aalten D.M., Alessi D.R.; RT "PDK1, the master regulator of AGC kinase signal transduction."; RL Semin. Cell Dev. Biol. 15:161-170(2004). RN [25] RP FUNCTION IN PHOSPHORYLATION OF IKKB, AND INTERACTION WITH IKKB. RX PubMed=16207722; DOI=10.1074/jbc.m506235200; RA Tanaka H., Fujita N., Tsuruo T.; RT "3-Phosphoinositide-dependent protein kinase-1-mediated IkappaB kinase beta RT (IkkB) phosphorylation activates NF-kappaB signaling."; RL J. Biol. Chem. 280:40965-40973(2005). RN [26] RP FUNCTION, ACTIVITY REGULATION, AND INTERACTION WITH STRAP. RX PubMed=16251192; DOI=10.1074/jbc.m507539200; RA Seong H.A., Jung H., Choi H.S., Kim K.T., Ha H.; RT "Regulation of transforming growth factor-beta signaling and PDK1 kinase RT activity by physical interaction between PDK1 and serine-threonine kinase RT receptor-associated protein."; RL J. Biol. Chem. 280:42897-42908(2005). RN [27] RP PHOSPHORYLATION AT SER-396, AND SUBCELLULAR LOCATION. RX PubMed=15743829; DOI=10.1128/mcb.25.6.2347-2363.2005; RA Scheid M.P., Parsons M., Woodgett J.R.; RT "Phosphoinositide-dependent phosphorylation of PDK1 regulates nuclear RT translocation."; RL Mol. Cell. Biol. 25:2347-2363(2005). RN [28] RP PHOSPHORYLATION AT TYR-9; TYR-373 AND TYR-376 BY INSR, AND INTERACTION WITH RP INSR. RX PubMed=16314505; DOI=10.1128/mcb.25.24.10803-10814.2005; RA Fiory F., Alberobello A.T., Miele C., Oriente F., Esposito I., Corbo V., RA Ruvo M., Tizzano B., Rasmussen T.E., Gammeltoft S., Formisano P., RA Beguinot F.; RT "Tyrosine phosphorylation of phosphoinositide-dependent kinase 1 by the RT insulin receptor is necessary for insulin metabolic signaling."; RL Mol. Cell. Biol. 25:10803-10814(2005). RN [29] RP PHOSPHORYLATION AT SER-241 AND THR-513. RX PubMed=16780920; DOI=10.1016/j.bioorg.2006.05.002; RA Gao X., Harris T.K.; RT "Role of the PH domain in regulating in vitro autophosphorylation events RT required for reconstitution of PDK1 catalytic activity."; RL Bioorg. Chem. 34:200-223(2006). RN [30] RP FUNCTION, AND INTERACTION WITH SMAD2; SMAD3; SMAD4 AND SMAD7. RX PubMed=17327236; DOI=10.1074/jbc.m609279200; RA Seong H.A., Jung H., Kim K.T., Ha H.; RT "3-Phosphoinositide-dependent PDK1 negatively regulates transforming growth RT factor-beta-induced signaling in a kinase-dependent manner through physical RT interaction with Smad proteins."; RL J. Biol. Chem. 282:12272-12289(2007). RN [31] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=17371830; DOI=10.1083/jcb.200607053; RA Primo L., di Blasio L., Roca C., Droetto S., Piva R., Schaffhausen B., RA Bussolino F.; RT "Essential role of PDK1 in regulating endothelial cell migration."; RL J. Cell Biol. 176:1035-1047(2007). RN [32] RP FUNCTION IN PHOSPHORYLATION OF PKN2. RX PubMed=18835241; DOI=10.1016/j.abb.2008.09.008; RA Lim W.G., Chen X., Liu J.P., Tan B.J., Zhou S., Smith A., Lees N., Hou L., RA Gu F., Yu X.Y., Du Y., Smith D., Verma C., Liu K., Duan W.; RT "The C-terminus of PRK2/PKNgamma is required for optimal activation by RhoA RT in a GTP-dependent manner."; RL Arch. Biochem. Biophys. 479:170-178(2008). RN [33] RP INTERACTION WITH NPRL2, AND ACTIVITY REGULATION. RX PubMed=18616680; DOI=10.1111/j.1349-7006.2008.00874.x; RA Kurata A., Katayama R., Watanabe T., Tsuruo T., Fujita N.; RT "TUSC4/NPRL2, a novel PDK1-interacting protein, inhibits PDK1 tyrosine RT phosphorylation and its downstream signaling."; RL Cancer Sci. 99:1827-1834(2008). RN [34] RP REVIEW ON FUNCTION. RX PubMed=18802401; DOI=10.4161/cc.7.19.6810; RA Bayascas J.R.; RT "Dissecting the role of the 3-phosphoinositide-dependent protein kinase-1 RT (PDK1) signalling pathways."; RL Cell Cycle 7:2978-2982(2008). RN [35] RP INTERACTION WITH SRC; RASA1 AND CRK, SUBCELLULAR LOCATION, AND TISSUE RP SPECIFICITY. RX PubMed=18024423; DOI=10.1074/jbc.m706361200; RA Yang K.J., Shin S., Piao L., Shin E., Li Y., Park K.A., Byun H.S., Won M., RA Hong J., Kweon G.R., Hur G.M., Seok J.H., Chun T., Brazil D.P., RA Hemmings B.A., Park J.; RT "Regulation of 3-phosphoinositide-dependent protein kinase-1 (PDK1) by Src RT involves tyrosine phosphorylation of PDK1 and Src homology 2 domain RT binding."; RL J. Biol. Chem. 283:1480-1491(2008). RN [36] RP SUBCELLULAR LOCATION, AND INTERACTION WITH PTPN6. RX PubMed=19591923; DOI=10.1016/j.cellsig.2009.06.010; RA Sephton C.F., Zhang D., Lehmann T.M., Pennington P.R., Scheid M.P., RA Mousseau D.D.; RT "The nuclear localization of 3'-phosphoinositide-dependent kinase-1 is RT dependent on its association with the protein tyrosine phosphatase SHP-1."; RL Cell. Signal. 21:1634-1644(2009). RN [37] RP SUBCELLULAR LOCATION. RX PubMed=19276999; DOI=10.1097/wnr.0b013e328329a41a; RA Alajajian B.B., Fletcher L., Isgor E., Jimenez D.F., Digicaylioglu M.; RT "IGF-I regulated phosphorylation and translocation of PDK-1 in neurons."; RL NeuroReport 20:579-583(2009). RN [38] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE 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 [39] RP PHOSPHORYLATION AT THR-354 BY MELK, PHOSPHORYLATION AT SER-394 AND SER-398 RP BY MAP3K5, AND MUTAGENESIS OF THR-354; SER-394 AND SER-398. RX PubMed=22544756; DOI=10.1074/jbc.m111.331827; RA Seong H.A., Jung H., Manoharan R., Ha H.; RT "PDK1 phosphorylation at Thr354 by murine protein serine/threonine kinase RT 38 contributes to the negative regulation of PDK1 activity."; RL J. Biol. Chem. 287:20811-20822(2012). RN [40] RP UBIQUITINATION, AND DEUBIQUITINATION BY USP4. RX PubMed=22347420; DOI=10.1371/journal.pone.0031003; RA Uras I.Z., List T., Nijman S.M.; RT "Ubiquitin-specific protease 4 inhibits mono-ubiquitination of the master RT growth factor signaling kinase PDK1."; RL PLoS ONE 7:E31003-E31003(2012). RN [41] RP IDENTIFICATION BY 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 [42] RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 71-359 IN COMPLEX WITH ATP. RX PubMed=12169624; DOI=10.1093/emboj/cdf437; RA Biondi R.M., Komander D., Thomas C.C., Lizcano J.M., Deak M., Alessi D.R., RA van Aalten D.M.; RT "High resolution crystal structure of the human PDK1 catalytic domain RT defines the regulatory phosphopeptide docking site."; RL EMBO J. 21:4219-4228(2002). RN [43] RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 51-360 IN COMPLEX WITH ATP. RX PubMed=15741170; DOI=10.1074/jbc.m500977200; RA Komander D., Kular G., Deak M., Alessi D.R., van Aalten D.M.; RT "Role of T-loop phosphorylation in PDK1 activation, stability, and RT substrate binding."; RL J. Biol. Chem. 280:18797-18802(2005). RN [44] RP X-RAY CRYSTALLOGRAPHY (2.17 ANGSTROMS) OF 74-359, AND PHOSPHORYLATION AT RP SER-241. RX PubMed=15772071; DOI=10.1074/jbc.m501367200; RA Feldman R.I., Wu J.M., Polokoff M.A., Kochanny M.J., Dinter H., Zhu D., RA Biroc S.L., Alicke B., Bryant J., Yuan S., Buckman B.O., Lentz D., RA Ferrer M., Whitlow M., Adler M., Finster S., Chang Z., Arnaiz D.O.; RT "Novel small molecule inhibitors of 3-phosphoinositide-dependent RT kinase-1."; RL J. Biol. Chem. 280:19867-19874(2005). RN [45] RP X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 409-556, SUBUNIT, ACTIVITY RP REGULATION, AND MUTAGENESIS OF THR-513. RX PubMed=20978239; DOI=10.1126/scisignal.2000738; RA Masters T.A., Calleja V., Armoogum D.A., Marsh R.J., Applebee C.J., RA Laguerre M., Bain A.J., Larijani B.; RT "Regulation of 3-phosphoinositide-dependent protein kinase 1 activity by RT homodimerization in live cells."; RL Sci. Signal. 3:RA78-RA78(2010). RN [46] RP X-RAY CRYSTALLOGRAPHY (1.43 ANGSTROMS) OF 51-359 IN COMPLEX WITH ATP, AND RP DOMAIN. RX PubMed=22999883; DOI=10.1016/j.chembiol.2012.07.017; RA Busschots K., Lopez-Garcia L.A., Lammi C., Stroba A., Zeuzem S., Piiper A., RA Alzari P.M., Neimanis S., Arencibia J.M., Engel M., Schulze J.O., RA Biondi R.M.; RT "Substrate-selective inhibition of protein kinase PDK1 by small compounds RT that bind to the PIF-pocket allosteric docking site."; RL Chem. Biol. 19:1152-1163(2012). CC -!- FUNCTION: Serine/threonine kinase which acts as a master kinase, CC phosphorylating and activating a subgroup of the AGC family of protein CC kinases. Its targets include: protein kinase B (PKB/AKT1, PKB/AKT2, CC PKB/AKT3), p70 ribosomal protein S6 kinase (RPS6KB1), p90 ribosomal CC protein S6 kinase (RPS6KA1, RPS6KA2 and RPS6KA3), cyclic AMP-dependent CC protein kinase (PRKACA), protein kinase C (PRKCD and PRKCZ), serum and CC glucocorticoid-inducible kinase (SGK1, SGK2 and SGK3), p21-activated CC kinase-1 (PAK1), protein kinase PKN (PKN1 and PKN2). Plays a central CC role in the transduction of signals from insulin by providing the CC activating phosphorylation to PKB/AKT1, thus propagating the signal to CC downstream targets controlling cell proliferation and survival, as well CC as glucose and amino acid uptake and storage. Negatively regulates the CC TGF-beta-induced signaling by: modulating the association of SMAD3 and CC SMAD7 with TGF-beta receptor, phosphorylating SMAD2, SMAD3, SMAD4 and CC SMAD7, preventing the nuclear translocation of SMAD3 and SMAD4 and the CC translocation of SMAD7 from the nucleus to the cytoplasm in response to CC TGF-beta. Activates PPARG transcriptional activity and promotes CC adipocyte differentiation. Activates the NF-kappa-B pathway via CC phosphorylation of IKKB. The tyrosine phosphorylated form is crucial CC for the regulation of focal adhesions by angiotensin II. Controls CC proliferation, survival, and growth of developing pancreatic cells. CC Participates in the regulation of Ca(2+) entry and Ca(2+)-activated CC K(+) channels of mast cells. Essential for the motility of vascular CC endothelial cells (ECs) and is involved in the regulation of their CC chemotaxis. Plays a critical role in cardiac homeostasis by serving as CC a dual effector for cell survival and beta-adrenergic response. Plays CC an important role during thymocyte development by regulating the CC expression of key nutrient receptors on the surface of pre-T cells and CC mediating Notch-induced cell growth and proliferative responses. CC Provides negative feedback inhibition to toll-like receptor-mediated CC NF-kappa-B activation in macrophages. Isoform 3 is catalytically CC inactive. {ECO:0000269|PubMed:10226025, ECO:0000269|PubMed:10480933, CC ECO:0000269|PubMed:10995762, ECO:0000269|PubMed:12167717, CC ECO:0000269|PubMed:14585963, ECO:0000269|PubMed:14604990, CC ECO:0000269|PubMed:16207722, ECO:0000269|PubMed:16251192, CC ECO:0000269|PubMed:17327236, ECO:0000269|PubMed:17371830, CC ECO:0000269|PubMed:18835241, ECO:0000269|PubMed:9094314, CC ECO:0000269|PubMed:9445476, ECO:0000269|PubMed:9707564, CC ECO:0000269|PubMed:9768361}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1; CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; CC EC=2.7.11.1; CC -!- ACTIVITY REGULATION: Homodimerization regulates its activity by CC maintaining the kinase in an autoinhibitory conformation. NPRL2 down- CC regulates its activity by interfering with tyrosine phosphorylation at CC the Tyr-9, Tyr-373 and Tyr-376 residues. The 14-3-3 protein YWHAQ acts CC as a negative regulator by association with the residues surrounding CC the Ser-241 residue. STRAP positively regulates its activity by CC enhancing its autophosphorylation and by stimulating its dissociation CC from YWHAQ. SMAD2, SMAD3, SMAD4 and SMAD7 also positively regulate its CC activity by stimulating its dissociation from YWHAQ. Activated by CC phosphorylation on Tyr-9, Tyr-373 and Tyr-376 by INSR in response to CC insulin. {ECO:0000269|PubMed:12177059, ECO:0000269|PubMed:16251192, CC ECO:0000269|PubMed:18616680, ECO:0000269|PubMed:20978239}. CC -!- SUBUNIT: Homodimer in its autoinhibited state. Active as monomer. CC Interacts with NPRL2, PPARG, PAK1, PTK2B, GRB14, PKN1 (via C-terminus), CC STRAP and IKKB. The Tyr-9 phosphorylated form interacts with SRC, RASA1 CC and CRK (via their SH2 domains). Interacts with SGK3 in a CC phosphorylation-dependent manner. The tyrosine-phosphorylated form CC interacts with PTPN6. The Ser-241 phosphorylated form interacts with CC YWHAH and YWHAQ. Binds INSR in response to insulin. Interacts (via PH CC domain) with SMAD3, SMAD4 and SMAD7. Interacts with PKN2; the CC interaction stimulates PDPK1 autophosphorylation, its PI(3,4,5)P3- CC dependent kinase activity toward 'Ser-473' of AKT1 but also activates CC its kinase activity toward PRKCD and PRKCZ. CC {ECO:0000269|PubMed:10226025, ECO:0000269|PubMed:10995762, CC ECO:0000269|PubMed:12177059, ECO:0000269|PubMed:14585963, CC ECO:0000269|PubMed:14604990, ECO:0000269|PubMed:15210700, CC ECO:0000269|PubMed:16207722, ECO:0000269|PubMed:16251192, CC ECO:0000269|PubMed:16314505, ECO:0000269|PubMed:17327236, CC ECO:0000269|PubMed:18024423, ECO:0000269|PubMed:18616680, CC ECO:0000269|PubMed:19591923, ECO:0000269|PubMed:20978239}. CC -!- INTERACTION: CC O15530; P31749: AKT1; NbExp=4; IntAct=EBI-717097, EBI-296087; CC O15530; Q00005: PPP2R2B; NbExp=8; IntAct=EBI-717097, EBI-1052159; CC O15530; O75385: ULK1; NbExp=2; IntAct=EBI-717097, EBI-908831; CC O15530-4; P54252: ATXN3; NbExp=3; IntAct=EBI-9087775, EBI-946046; CC O15530-4; P42858: HTT; NbExp=6; IntAct=EBI-9087775, EBI-466029; CC O15530-4; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-9087775, EBI-1055254; CC O15530-4; Q8IUH5: ZDHHC17; NbExp=3; IntAct=EBI-9087775, EBI-524753; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Cell membrane; Peripheral CC membrane protein. Cell junction, focal adhesion. Note=Tyrosine CC phosphorylation seems to occur only at the cell membrane. Translocates CC to the cell membrane following insulin stimulation by a mechanism that CC involves binding to GRB14 and INSR. SRC and HSP90 promote its CC localization to the cell membrane. Its nuclear localization is CC dependent on its association with PTPN6 and its phosphorylation at Ser- CC 396. Restricted to the nucleus in neuronal cells while in non-neuronal CC cells it is found in the cytoplasm. The Ser-241 phosphorylated form is CC distributed along the perinuclear region in neuronal cells while in CC non-neuronal cells it is found in both the nucleus and the cytoplasm. CC IGF1 transiently increases phosphorylation at Ser-241 of neuronal CC PDPK1, resulting in its translocation to other cellular compartments. CC The tyrosine-phosphorylated form colocalizes with PTK2B in focal CC adhesions after angiotensin II stimulation. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=1; CC IsoId=O15530-1; Sequence=Displayed; CC Name=2; CC IsoId=O15530-2; Sequence=VSP_004894; CC Name=3; CC IsoId=O15530-3; Sequence=VSP_004895; CC Name=4; CC IsoId=O15530-4; Sequence=VSP_041902; CC Name=5; CC IsoId=O15530-5; Sequence=VSP_044796; CC -!- TISSUE SPECIFICITY: Appears to be expressed ubiquitously. The Tyr-9 CC phosphorylated form is markedly increased in diseased tissue compared CC with normal tissue from lung, liver, colon and breast. CC {ECO:0000269|PubMed:18024423}. CC -!- INDUCTION: Stimulated by insulin, and the oxidants hydrogen peroxide CC and peroxovanadate. CC -!- DOMAIN: The PH domain plays a pivotal role in the localization and CC nuclear import of PDPK1 and is also essential for its homodimerization. CC -!- DOMAIN: The PIF-pocket is a small lobe in the catalytic domain required CC by the enzyme for the binding to the hydrophobic motif of its CC substrates. It is an allosteric regulatory site that can accommodate CC small compounds acting as allosteric inhibitors. CC {ECO:0000305|PubMed:22999883}. CC -!- PTM: Phosphorylation on Ser-241 in the activation loop is required for CC full activity. PDPK1 itself can autophosphorylate Ser-241, leading to CC its own activation. Autophosphorylation is inhibited by the apoptotic CC C-terminus cleavage product of PKN2 (By similarity). Tyr-9 CC phosphorylation is critical for stabilization of both PDPK1 and the CC PDPK1/SRC complex via HSP90-mediated protection of PDPK1 degradation. CC Angiotensin II stimulates the tyrosine phosphorylation of PDPK1 in CC vascular smooth muscle in a calcium- and SRC-dependent manner. CC Phosphorylated on Tyr-9, Tyr-373 and Tyr-376 by INSR in response to CC insulin. Palmitate negatively regulates autophosphorylation at Ser-241 CC and palmitate-induced phosphorylation at Ser-529 and Ser-501 by CC PKC/PRKCQ negatively regulates its ability to phosphorylate PKB/AKT1. CC Phosphorylation at Thr-354 by MELK partially inhibits kinase activity, CC the inhibition is cooperatively enhanced by phosphorylation at Ser-394 CC and Ser-398 by MAP3K5. {ECO:0000250, ECO:0000269|PubMed:10455013, CC ECO:0000269|PubMed:11481331, ECO:0000269|PubMed:14585963, CC ECO:0000269|PubMed:15743829, ECO:0000269|PubMed:16314505, CC ECO:0000269|PubMed:16780920, ECO:0000269|PubMed:22544756, CC ECO:0000269|Ref.8}. CC -!- PTM: Autophosphorylated; autophosphorylation is inhibited by the CC apoptotic C-terminus cleavage product of PKN2. {ECO:0000250}. CC -!- PTM: Monoubiquitinated in the kinase domain, deubiquitinated by USP4. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr CC protein kinase family. PDPK1 subfamily. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAD93072.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF017995; AAC51825.1; -; mRNA. DR EMBL; Y15056; CAA75341.1; -; mRNA. DR EMBL; CR536517; CAG38755.1; -; mRNA. DR EMBL; AB209835; BAD93072.1; ALT_INIT; mRNA. DR EMBL; AC093525; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC141586; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC006339; AAH06339.2; -; mRNA. DR EMBL; BC012103; AAH12103.1; -; mRNA. DR EMBL; BC033494; AAH33494.1; -; mRNA. DR CCDS; CCDS10472.1; -. [O15530-1] DR CCDS; CCDS10473.1; -. [O15530-4] DR CCDS; CCDS58411.1; -. [O15530-5] DR RefSeq; NP_001248745.1; NM_001261816.1. [O15530-5] DR RefSeq; NP_002604.1; NM_002613.4. [O15530-1] DR RefSeq; NP_112558.2; NM_031268.5. [O15530-4] DR PDB; 1H1W; X-ray; 2.00 A; A=71-359. DR PDB; 1OKY; X-ray; 2.30 A; A=51-360. DR PDB; 1OKZ; X-ray; 2.51 A; A=51-360. DR PDB; 1UU3; X-ray; 1.70 A; A=51-360. DR PDB; 1UU7; X-ray; 1.90 A; A=51-360. DR PDB; 1UU8; X-ray; 2.50 A; A=51-360. DR PDB; 1UU9; X-ray; 1.95 A; A=72-357. DR PDB; 1UVR; X-ray; 2.81 A; A=71-359. DR PDB; 1W1D; X-ray; 1.50 A; A=409-556. DR PDB; 1W1G; X-ray; 1.45 A; A=409-556. DR PDB; 1W1H; X-ray; 1.45 A; A/B/C/D=409-556. DR PDB; 1Z5M; X-ray; 2.17 A; A=74-359. DR PDB; 2BIY; X-ray; 1.95 A; A=51-360. DR PDB; 2PE0; X-ray; 2.35 A; A=74-359. DR PDB; 2PE1; X-ray; 2.14 A; A=74-359. DR PDB; 2PE2; X-ray; 2.13 A; A=74-359. DR PDB; 2R7B; X-ray; 2.70 A; A=48-359. DR PDB; 2VKI; X-ray; 1.80 A; A=409-556. DR PDB; 2XCH; X-ray; 2.00 A; A=51-359. DR PDB; 2XCK; X-ray; 2.30 A; A=51-359. DR PDB; 3H9O; X-ray; 2.30 A; A=51-359. DR PDB; 3HRC; X-ray; 1.91 A; A=50-359. DR PDB; 3HRF; X-ray; 1.90 A; A=50-359. DR PDB; 3ION; X-ray; 2.40 A; A=48-359. DR PDB; 3IOP; X-ray; 2.20 A; A=48-359. DR PDB; 3NAX; X-ray; 1.75 A; A=66-362. DR PDB; 3NAY; X-ray; 2.60 A; A/B=66-362. DR PDB; 3NUN; X-ray; 2.20 A; A=67-358. DR PDB; 3NUS; X-ray; 2.75 A; A=73-358. DR PDB; 3NUU; X-ray; 1.98 A; A=73-358. DR PDB; 3NUY; X-ray; 2.10 A; A=73-358. DR PDB; 3ORX; X-ray; 2.20 A; A/B/C/D/E/F/G/H=51-359. DR PDB; 3ORZ; X-ray; 2.00 A; A/B/C/D=51-359. DR PDB; 3OTU; X-ray; 2.10 A; A=51-359. DR PDB; 3PWY; X-ray; 3.50 A; A=51-359. DR PDB; 3QC4; X-ray; 1.80 A; A/B=51-359. DR PDB; 3QCQ; X-ray; 2.50 A; A=48-359. DR PDB; 3QCS; X-ray; 2.49 A; A=48-359. DR PDB; 3QCX; X-ray; 2.30 A; A=48-359. DR PDB; 3QCY; X-ray; 2.20 A; A=48-359. DR PDB; 3QD0; X-ray; 1.99 A; A=48-359. DR PDB; 3QD3; X-ray; 2.00 A; A=48-359. DR PDB; 3QD4; X-ray; 2.30 A; A=48-359. DR PDB; 3RCJ; X-ray; 1.70 A; A=50-359. DR PDB; 3RWP; X-ray; 1.92 A; A=51-359. DR PDB; 3RWQ; X-ray; 2.55 A; A=51-359. DR PDB; 3SC1; X-ray; 2.70 A; A=50-359. DR PDB; 4A06; X-ray; 2.00 A; A=50-359. DR PDB; 4A07; X-ray; 1.85 A; A=50-359. DR PDB; 4AW0; X-ray; 1.43 A; A=51-359. DR PDB; 4AW1; X-ray; 1.68 A; A=51-359. DR PDB; 4CT1; X-ray; 1.85 A; A=50-359. DR PDB; 4CT2; X-ray; 1.25 A; A=50-359. DR PDB; 4RQK; X-ray; 1.55 A; A=50-359. DR PDB; 4RQV; X-ray; 1.50 A; A=50-359. DR PDB; 4RRV; X-ray; 1.41 A; A=50-359. DR PDB; 4XX9; X-ray; 1.40 A; A=50-359. DR PDB; 5ACK; X-ray; 1.24 A; A=50-359. DR PDB; 5HKM; X-ray; 2.10 A; A=51-359. DR PDB; 5HNG; X-ray; 3.01 A; A=51-359. DR PDB; 5HO7; X-ray; 3.00 A; A=51-359. DR PDB; 5HO8; X-ray; 2.70 A; A=51-359. DR PDB; 5LVL; X-ray; 1.40 A; A=50-359. DR PDB; 5LVM; X-ray; 1.26 A; A=50-359. DR PDB; 5LVN; X-ray; 1.38 A; A=50-359. DR PDB; 5LVO; X-ray; 1.09 A; A=50-359. DR PDB; 5LVP; X-ray; 2.50 A; A/B/C/D=50-359. DR PDB; 5MRD; X-ray; 1.41 A; A=50-359. DR PDB; 6WJQ; X-ray; 2.71 A; C/D=2-16. DR PDB; 8DQT; X-ray; 1.31 A; A=50-359. DR PDBsum; 1H1W; -. DR PDBsum; 1OKY; -. DR PDBsum; 1OKZ; -. DR PDBsum; 1UU3; -. DR PDBsum; 1UU7; -. DR PDBsum; 1UU8; -. DR PDBsum; 1UU9; -. DR PDBsum; 1UVR; -. DR PDBsum; 1W1D; -. DR PDBsum; 1W1G; -. DR PDBsum; 1W1H; -. DR PDBsum; 1Z5M; -. DR PDBsum; 2BIY; -. DR PDBsum; 2PE0; -. DR PDBsum; 2PE1; -. DR PDBsum; 2PE2; -. DR PDBsum; 2R7B; -. DR PDBsum; 2VKI; -. DR PDBsum; 2XCH; -. DR PDBsum; 2XCK; -. DR PDBsum; 3H9O; -. DR PDBsum; 3HRC; -. DR PDBsum; 3HRF; -. DR PDBsum; 3ION; -. DR PDBsum; 3IOP; -. DR PDBsum; 3NAX; -. DR PDBsum; 3NAY; -. DR PDBsum; 3NUN; -. DR PDBsum; 3NUS; -. DR PDBsum; 3NUU; -. DR PDBsum; 3NUY; -. DR PDBsum; 3ORX; -. DR PDBsum; 3ORZ; -. DR PDBsum; 3OTU; -. DR PDBsum; 3PWY; -. DR PDBsum; 3QC4; -. DR PDBsum; 3QCQ; -. DR PDBsum; 3QCS; -. DR PDBsum; 3QCX; -. DR PDBsum; 3QCY; -. DR PDBsum; 3QD0; -. DR PDBsum; 3QD3; -. DR PDBsum; 3QD4; -. DR PDBsum; 3RCJ; -. DR PDBsum; 3RWP; -. DR PDBsum; 3RWQ; -. DR PDBsum; 3SC1; -. DR PDBsum; 4A06; -. DR PDBsum; 4A07; -. DR PDBsum; 4AW0; -. DR PDBsum; 4AW1; -. DR PDBsum; 4CT1; -. DR PDBsum; 4CT2; -. DR PDBsum; 4RQK; -. DR PDBsum; 4RQV; -. DR PDBsum; 4RRV; -. DR PDBsum; 4XX9; -. DR PDBsum; 5ACK; -. DR PDBsum; 5HKM; -. DR PDBsum; 5HNG; -. DR PDBsum; 5HO7; -. DR PDBsum; 5HO8; -. DR PDBsum; 5LVL; -. DR PDBsum; 5LVM; -. DR PDBsum; 5LVN; -. DR PDBsum; 5LVO; -. DR PDBsum; 5LVP; -. DR PDBsum; 5MRD; -. DR PDBsum; 6WJQ; -. DR PDBsum; 8DQT; -. DR AlphaFoldDB; O15530; -. DR SASBDB; O15530; -. DR SMR; O15530; -. DR BioGRID; 111196; 187. DR DIP; DIP-38372N; -. DR ELM; O15530; -. DR IntAct; O15530; 144. DR MINT; O15530; -. DR STRING; 9606.ENSP00000344220; -. DR BindingDB; O15530; -. DR ChEMBL; CHEMBL2534; -. DR DrugBank; DB07132; 1-{2-OXO-3-[(1R)-1-(1H-PYRROL-2-YL)ETHYL]-2H-INDOL-5-YL}UREA. DR DrugBank; DB06932; 10,11-dimethoxy-4-methyldibenzo[c,f]-2,7-naphthyridine-3,6-diamine. DR DrugBank; DB07300; 2-(1H-imidazol-1-yl)-9-methoxy-8-(2-methoxyethoxy)benzo[c][2,7]naphthyridin-4-amine. DR DrugBank; DB07456; 3-(1H-indol-3-yl)-4-(1-{2-[(2S)-1-methylpyrrolidinyl]ethyl}-1H-indol-3-yl)-1H-pyrrole-2,5-dione. DR DrugBank; DB07457; 3-[1-(3-AMINOPROPYL)-1H-INDOL-3-YL]-4-(1H-INDOL-3-YL)-1H-PYRROLE-2,5-DIONE. DR DrugBank; DB07033; 5-HYDROXY-3-[(1R)-1-(1H-PYRROL-2-YL)ETHYL]-2H-INDOL-2-ONE. DR DrugBank; DB01933; 7-Hydroxystaurosporine. DR DrugBank; DB03777; Bisindolylmaleimide I. DR DrugBank; DB01946; Bisindolylmaleimide VIII. DR DrugBank; DB00482; Celecoxib. DR DrugBank; DB04522; Dexfosfoserine. DR DrugBank; DB12010; Fostamatinib. DR DrugBank; DB01863; Inositol 1,3,4,5-Tetrakisphosphate. DR DrugBank; DB02010; Staurosporine. DR DrugCentral; O15530; -. DR GuidetoPHARMACOLOGY; 1519; -. DR MoonDB; O15530; Predicted. DR GlyGen; O15530; 18 sites, 1 O-linked glycan (18 sites). DR iPTMnet; O15530; -. DR PhosphoSitePlus; O15530; -. DR BioMuta; PDPK1; -. DR CPTAC; CPTAC-1052; -. DR CPTAC; CPTAC-1540; -. DR EPD; O15530; -. DR jPOST; O15530; -. DR MassIVE; O15530; -. DR MaxQB; O15530; -. DR PaxDb; 9606-ENSP00000344220; -. DR PeptideAtlas; O15530; -. DR ProteomicsDB; 34858; -. DR ProteomicsDB; 48736; -. [O15530-1] DR ProteomicsDB; 48737; -. [O15530-2] DR ProteomicsDB; 48738; -. [O15530-3] DR ProteomicsDB; 48739; -. [O15530-4] DR Pumba; O15530; -. DR Antibodypedia; 3794; 1207 antibodies from 47 providers. DR DNASU; 5170; -. DR Ensembl; ENST00000268673.11; ENSP00000268673.7; ENSG00000140992.19. [O15530-4] DR Ensembl; ENST00000342085.9; ENSP00000344220.4; ENSG00000140992.19. [O15530-1] DR Ensembl; ENST00000441549.7; ENSP00000395357.3; ENSG00000140992.19. [O15530-5] DR GeneID; 5170; -. DR KEGG; hsa:5170; -. DR MANE-Select; ENST00000342085.9; ENSP00000344220.4; NM_002613.5; NP_002604.1. DR UCSC; uc002cqs.5; human. [O15530-1] DR AGR; HGNC:8816; -. DR CTD; 5170; -. DR DisGeNET; 5170; -. DR GeneCards; PDPK1; -. DR HGNC; HGNC:8816; PDPK1. DR HPA; ENSG00000140992; Low tissue specificity. DR MIM; 605213; gene. DR neXtProt; NX_O15530; -. DR OpenTargets; ENSG00000140992; -. DR PharmGKB; PA33160; -. DR VEuPathDB; HostDB:ENSG00000140992; -. DR eggNOG; KOG0592; Eukaryota. DR GeneTree; ENSGT00940000155267; -. DR InParanoid; O15530; -. DR OMA; GYPSIRA; -. DR OrthoDB; 208777at2759; -. DR PhylomeDB; O15530; -. DR TreeFam; TF105423; -. DR BRENDA; 2.7.11.1; 2681. DR PathwayCommons; O15530; -. DR Reactome; R-HSA-114604; GPVI-mediated activation cascade. DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling. DR Reactome; R-HSA-165158; Activation of AKT2. DR Reactome; R-HSA-202424; Downstream TCR signaling. DR Reactome; R-HSA-2730905; Role of LAT2/NTAL/LAB on calcium mobilization. DR Reactome; R-HSA-2871837; FCERI mediated NF-kB activation. DR Reactome; R-HSA-354192; Integrin signaling. DR Reactome; R-HSA-389357; CD28 dependent PI3K/Akt signaling. DR Reactome; R-HSA-392451; G beta:gamma signalling through PI3Kgamma. DR Reactome; R-HSA-444257; RSK activation. DR Reactome; R-HSA-5218920; VEGFR2 mediated vascular permeability. DR Reactome; R-HSA-5218921; VEGFR2 mediated cell proliferation. DR Reactome; R-HSA-5607764; CLEC7A (Dectin-1) signaling. DR Reactome; R-HSA-5625740; RHO GTPases activate PKNs. DR Reactome; R-HSA-5674400; Constitutive Signaling by AKT1 E17K in Cancer. DR Reactome; R-HSA-6804757; Regulation of TP53 Degradation. DR Reactome; R-HSA-9634635; Estrogen-stimulated signaling through PRKCZ. DR Reactome; R-HSA-9735871; SARS-CoV-1 targets host intracellular signalling and regulatory pathways. DR Reactome; R-HSA-9755779; SARS-CoV-2 targets host intracellular signalling and regulatory pathways. DR SABIO-RK; O15530; -. DR SignaLink; O15530; -. DR SIGNOR; O15530; -. DR BioGRID-ORCS; 5170; 578 hits in 1207 CRISPR screens. DR ChiTaRS; PDPK1; human. DR EvolutionaryTrace; O15530; -. DR GeneWiki; Phosphoinositide-dependent_kinase-1; -. DR GenomeRNAi; 5170; -. DR Pharos; O15530; Tchem. DR PRO; PR:O15530; -. DR Proteomes; UP000005640; Chromosome 16. DR RNAct; O15530; Protein. DR Bgee; ENSG00000140992; Expressed in secondary oocyte and 196 other cell types or tissues. DR ExpressionAtlas; O15530; baseline and differential. DR GO; GO:0042995; C:cell projection; IDA:BHF-UCL. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:Ensembl. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005925; C:focal adhesion; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0014069; C:postsynaptic density; IEA:Ensembl. DR GO; GO:0004676; F:3-phosphoinositide-dependent protein kinase activity; IDA:BHF-UCL. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0016004; F:phospholipase activator activity; IMP:BHF-UCL. DR GO; GO:0043274; F:phospholipase binding; IPI:BHF-UCL. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:BHF-UCL. DR GO; GO:0030036; P:actin cytoskeleton organization; TAS:ProtInc. DR GO; GO:0032148; P:activation of protein kinase B activity; IDA:BHF-UCL. DR GO; GO:0019722; P:calcium-mediated signaling; IMP:BHF-UCL. DR GO; GO:0016477; P:cell migration; IMP:BHF-UCL. DR GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; IMP:BHF-UCL. DR GO; GO:0032869; P:cellular response to insulin stimulus; IMP:BHF-UCL. DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IMP:BHF-UCL. DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; IMP:UniProtKB. DR GO; GO:0006972; P:hyperosmotic response; IEA:Ensembl. DR GO; GO:0008286; P:insulin receptor signaling pathway; IEA:Ensembl. DR GO; GO:0048009; P:insulin-like growth factor receptor signaling pathway; IEA:Ensembl. DR GO; GO:0035556; P:intracellular signal transduction; IDA:MGI. DR GO; GO:0010667; P:negative regulation of cardiac muscle cell apoptotic process; IEA:Ensembl. DR GO; GO:2000352; P:negative regulation of endothelial cell apoptotic process; IMP:BHF-UCL. DR GO; GO:0006469; P:negative regulation of protein kinase activity; IDA:BHF-UCL. DR GO; GO:0034122; P:negative regulation of toll-like receptor signaling pathway; IEA:Ensembl. DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IDA:BHF-UCL. DR GO; GO:0045766; P:positive regulation of angiogenesis; IMP:BHF-UCL. DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; IMP:BHF-UCL. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; TAS:Reactome. DR GO; GO:0010518; P:positive regulation of phospholipase activity; IMP:BHF-UCL. DR GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; IMP:BHF-UCL. DR GO; GO:0051281; P:positive regulation of release of sequestered calcium ion into cytosol; IDA:BHF-UCL. DR GO; GO:1903672; P:positive regulation of sprouting angiogenesis; IMP:BHF-UCL. DR GO; GO:1905564; P:positive regulation of vascular endothelial cell proliferation; IMP:BHF-UCL. DR GO; GO:0046777; P:protein autophosphorylation; TAS:UniProtKB. DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB. DR GO; GO:0043122; P:regulation of canonical NF-kappaB signal transduction; IMP:UniProtKB. DR GO; GO:0043304; P:regulation of mast cell degranulation; IEA:Ensembl. DR GO; GO:0031295; P:T cell costimulation; TAS:Reactome. DR GO; GO:0003323; P:type B pancreatic cell development; IEA:Ensembl. DR CDD; cd01262; PH_PDK1; 1. DR CDD; cd05581; STKc_PDK1; 1. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR033931; PDK1-typ_PH. DR InterPro; IPR039046; PDPK1. DR InterPro; IPR011993; PH-like_dom_sf. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR PANTHER; PTHR24356:SF163; 3-PHOSPHOINOSITIDE-DEPENDENT PROTEIN KINASE 1-RELATED; 1. DR PANTHER; PTHR24356; SERINE/THREONINE-PROTEIN KINASE; 1. DR Pfam; PF14593; PH_3; 1. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF50729; PH domain-like; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR Genevisible; O15530; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Activator; Alternative splicing; ATP-binding; KW Cell junction; Cell membrane; Cytoplasm; Direct protein sequencing; Kinase; KW Membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; KW Serine/threonine-protein kinase; Transcription; Transcription regulation; KW Transferase; Ubl conjugation. FT CHAIN 1..556 FT /note="3-phosphoinositide-dependent protein kinase 1" FT /id="PRO_0000086500" FT DOMAIN 82..342 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT DOMAIN 459..550 FT /note="PH" FT REGION 26..80 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 113..157 FT /note="PIF-pocket" FT /evidence="ECO:0000305|PubMed:22999883" FT COMPBIAS 26..42 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 205 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10027" FT BINDING 92..94 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:12169624, FT ECO:0000269|PubMed:15741170, ECO:0000269|PubMed:22999883" FT BINDING 111 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:12169624, FT ECO:0000269|PubMed:15741170, ECO:0000269|PubMed:22999883" FT BINDING 160..162 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:12169624, FT ECO:0000269|PubMed:15741170, ECO:0000269|PubMed:22999883" FT BINDING 166 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:12169624, FT ECO:0000269|PubMed:15741170, ECO:0000269|PubMed:22999883" FT BINDING 209 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:22999883" FT BINDING 223 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:12169624, FT ECO:0000269|PubMed:15741170, ECO:0000269|PubMed:22999883" FT MOD_RES 9 FT /note="Phosphotyrosine; by SRC and INSR" FT /evidence="ECO:0000269|PubMed:11481331, FT ECO:0000269|PubMed:14585963, ECO:0000269|PubMed:16314505" FT MOD_RES 25 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:10455013" FT MOD_RES 241 FT /note="Phosphoserine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:10455013, FT ECO:0000269|PubMed:11481331, ECO:0000269|PubMed:15772071, FT ECO:0000269|PubMed:16780920, ECO:0000269|Ref.8" FT MOD_RES 304 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q9Z2A0" FT MOD_RES 354 FT /note="Phosphothreonine; by MELK" FT /evidence="ECO:0000269|PubMed:22544756" FT MOD_RES 373 FT /note="Phosphotyrosine; by SRC and INSR" FT /evidence="ECO:0000269|PubMed:11481331, FT ECO:0000269|PubMed:14585963, ECO:0000269|PubMed:16314505" FT MOD_RES 376 FT /note="Phosphotyrosine; by SRC and INSR" FT /evidence="ECO:0000269|PubMed:11481331, FT ECO:0000269|PubMed:14585963, ECO:0000269|PubMed:16314505" FT MOD_RES 393 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:10455013" FT MOD_RES 394 FT /note="Phosphoserine; by MAP3K5" FT /evidence="ECO:0000269|PubMed:22544756" FT MOD_RES 396 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:10455013, FT ECO:0000269|PubMed:15743829" FT MOD_RES 398 FT /note="Phosphoserine; by MAP3K5" FT /evidence="ECO:0000269|PubMed:22544756" FT MOD_RES 410 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:10455013" FT MOD_RES 501 FT /note="Phosphoserine; by PKC/PRKCQ" FT /evidence="ECO:0000250|UniProtKB:Q9Z2A0" FT MOD_RES 513 FT /note="Phosphothreonine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:16780920" FT MOD_RES 529 FT /note="Phosphoserine; by PKC/PRKCQ" FT /evidence="ECO:0000250|UniProtKB:Q9Z2A0" FT VAR_SEQ 1..50 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_004894" FT VAR_SEQ 110..237 FT /note="IKILEKRHIIKENKVPYVTRERDVMSRLDHPFFVKLYFTFQDDEKLYFGLSY FT AKNGELLKYIRKIGSFDETCTRFYTAEIVSALEYLHGKGIIHRDLKPENILLNEDMHIQ FT ITDFGTAKVLSPESKQA -> T (in isoform 4)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_041902" FT VAR_SEQ 238..263 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:9445477" FT /id="VSP_004895" FT VAR_SEQ 448..556 FT /note="WHQFVENNLILKMGPVDKRKGLFARRRQLLLTEGPHLYYVDPVNKVLKGEIP FT WSQELRPEAKNFKTFFVHTPNRTYYLMDPSGNAHKWCRKIQEVWRQRYQSHPDAAVQ FT -> CLTGRII (in isoform 5)" FT /evidence="ECO:0000303|Ref.5" FT /id="VSP_044796" FT MUTAGEN 9 FT /note="Y->F: Slight reduction in pervanadate-stimulated FT tyrosine phosphorylation." FT /evidence="ECO:0000269|PubMed:11481331" FT MUTAGEN 25 FT /note="S->A: No effect." FT /evidence="ECO:0000269|PubMed:10455013" FT MUTAGEN 241 FT /note="S->A: No activation." FT /evidence="ECO:0000269|PubMed:10455013" FT MUTAGEN 277 FT /note="A->V: 3-fold increase in kinase activity." FT /evidence="ECO:0000269|PubMed:10364160" FT MUTAGEN 354 FT /note="T->A: Abolishes phosphorylation by MELK." FT /evidence="ECO:0000269|PubMed:22544756" FT MUTAGEN 373 FT /note="Y->F: Reduction in basal activity." FT /evidence="ECO:0000269|PubMed:11481331" FT MUTAGEN 376 FT /note="Y->F: Reduction in basal activity." FT /evidence="ECO:0000269|PubMed:11481331" FT MUTAGEN 393 FT /note="S->A: No effect." FT /evidence="ECO:0000269|PubMed:10455013" FT MUTAGEN 394 FT /note="S->A: Abolishes phosphorylation by MAP3K5; when FT associated with A-398." FT /evidence="ECO:0000269|PubMed:22544756" FT MUTAGEN 396 FT /note="S->A: No effect." FT /evidence="ECO:0000269|PubMed:10455013" FT MUTAGEN 398 FT /note="S->A: Abolishes phosphorylation by MAP3K5; when FT associated with A-394." FT /evidence="ECO:0000269|PubMed:22544756" FT MUTAGEN 410 FT /note="S->A: No effect." FT /evidence="ECO:0000269|PubMed:10455013" FT MUTAGEN 474 FT /note="R->A: No PDGF-dependent translocation to the FT membrane." FT /evidence="ECO:0000269|PubMed:9637919" FT MUTAGEN 513 FT /note="T->E: Enhanced kinase activity towards PKB." FT /evidence="ECO:0000269|PubMed:20978239" FT TURN 7..9 FT /evidence="ECO:0007829|PDB:6WJQ" FT HELIX 79..81 FT /evidence="ECO:0007829|PDB:5LVO" FT STRAND 82..90 FT /evidence="ECO:0007829|PDB:5LVO" FT STRAND 95..101 FT /evidence="ECO:0007829|PDB:5LVO" FT TURN 102..104 FT /evidence="ECO:0007829|PDB:5LVO" FT STRAND 107..114 FT /evidence="ECO:0007829|PDB:5LVO" FT HELIX 115..120 FT /evidence="ECO:0007829|PDB:5LVO" FT HELIX 124..136 FT /evidence="ECO:0007829|PDB:5LVO" FT STRAND 145..150 FT /evidence="ECO:0007829|PDB:5LVO" FT STRAND 152..159 FT /evidence="ECO:0007829|PDB:5LVO" FT STRAND 163..166 FT /evidence="ECO:0007829|PDB:3PWY" FT HELIX 167..174 FT /evidence="ECO:0007829|PDB:5LVO" FT HELIX 179..198 FT /evidence="ECO:0007829|PDB:5LVO" FT HELIX 208..210 FT /evidence="ECO:0007829|PDB:5LVO" FT STRAND 211..213 FT /evidence="ECO:0007829|PDB:5LVO" FT STRAND 219..221 FT /evidence="ECO:0007829|PDB:5LVO" FT HELIX 224..226 FT /evidence="ECO:0007829|PDB:3ORX" FT TURN 232..235 FT /evidence="ECO:0007829|PDB:5LVO" FT STRAND 238..240 FT /evidence="ECO:0007829|PDB:3OTU" FT HELIX 246..248 FT /evidence="ECO:0007829|PDB:5LVO" FT HELIX 251..256 FT /evidence="ECO:0007829|PDB:5LVO" FT HELIX 261..277 FT /evidence="ECO:0007829|PDB:5LVO" FT HELIX 287..295 FT /evidence="ECO:0007829|PDB:5LVO" FT STRAND 303..305 FT /evidence="ECO:0007829|PDB:3QD3" FT HELIX 307..316 FT /evidence="ECO:0007829|PDB:5LVO" FT HELIX 321..323 FT /evidence="ECO:0007829|PDB:5LVO" FT HELIX 328..330 FT /evidence="ECO:0007829|PDB:5LVO" FT HELIX 333..337 FT /evidence="ECO:0007829|PDB:5LVO" FT HELIX 340..342 FT /evidence="ECO:0007829|PDB:5LVO" FT HELIX 347..352 FT /evidence="ECO:0007829|PDB:5LVO" FT HELIX 412..415 FT /evidence="ECO:0007829|PDB:1W1G" FT STRAND 416..420 FT /evidence="ECO:0007829|PDB:1W1G" FT STRAND 423..426 FT /evidence="ECO:0007829|PDB:1W1G" FT HELIX 432..445 FT /evidence="ECO:0007829|PDB:1W1G" FT HELIX 449..451 FT /evidence="ECO:0007829|PDB:1W1G" FT TURN 452..454 FT /evidence="ECO:0007829|PDB:1W1G" FT STRAND 457..467 FT /evidence="ECO:0007829|PDB:1W1G" FT STRAND 470..479 FT /evidence="ECO:0007829|PDB:1W1G" FT TURN 480..482 FT /evidence="ECO:0007829|PDB:1W1G" FT STRAND 483..488 FT /evidence="ECO:0007829|PDB:1W1G" FT TURN 489..492 FT /evidence="ECO:0007829|PDB:1W1G" FT STRAND 493..498 FT /evidence="ECO:0007829|PDB:1W1G" FT STRAND 505..518 FT /evidence="ECO:0007829|PDB:1W1G" FT STRAND 521..526 FT /evidence="ECO:0007829|PDB:1W1G" FT HELIX 532..547 FT /evidence="ECO:0007829|PDB:1W1G" SQ SEQUENCE 556 AA; 63152 MW; ED8C0306DC4D0653 CRC64; MARTTSQLYD AVPIQSSVVL CSCPSPSMVR TQTESSTPPG IPGGSRQGPA MDGTAAEPRP GAGSLQHAQP PPQPRKKRPE DFKFGKILGE GSFSTVVLAR ELATSREYAI KILEKRHIIK ENKVPYVTRE RDVMSRLDHP FFVKLYFTFQ DDEKLYFGLS YAKNGELLKY IRKIGSFDET CTRFYTAEIV SALEYLHGKG IIHRDLKPEN ILLNEDMHIQ ITDFGTAKVL SPESKQARAN SFVGTAQYVS PELLTEKSAC KSSDLWALGC IIYQLVAGLP PFRAGNEYLI FQKIIKLEYD FPEKFFPKAR DLVEKLLVLD ATKRLGCEEM EGYGPLKAHP FFESVTWENL HQQTPPKLTA YLPAMSEDDE DCYGNYDNLL SQFGCMQVSS SSSSHSLSAS DTGLPQRSGS NIEQYIHDLD SNSFELDLQF SEDEKRLLLE KQAGGNPWHQ FVENNLILKM GPVDKRKGLF ARRRQLLLTE GPHLYYVDPV NKVLKGEIPW SQELRPEAKN FKTFFVHTPN RTYYLMDPSG NAHKWCRKIQ EVWRQRYQSH PDAAVQ //