ID PDPK1_MOUSE Reviewed; 559 AA. AC Q9Z2A0; A6H6U3; Q9R1D8; Q9R215; DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot. DT 18-OCT-2001, sequence version 2. DT 24-JAN-2024, entry version 200. DE RecName: Full=3-phosphoinositide-dependent protein kinase 1; DE Short=mPDK1; DE EC=2.7.11.1; GN Name=Pdpk1; Synonyms=Pdk1; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Liver; RX PubMed=10075713; DOI=10.1074/jbc.274.12.8117; RA Dong L.Q., Zhang R.-B., Langlais P., He H., Clark M., Zhu L., Liu F.; RT "Primary structure, tissue distribution, and expression of mouse RT phosphoinositide-dependent protein kinase-1, a protein kinase that RT phosphorylates and activates protein kinase C zeta."; RL J. Biol. Chem. 274:8117-8122(1999). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Brain; RA Park J., Hemmings B.A.; RT "Mouse phosphoinositide-dependent protein kinase 1 (mPDK1)."; RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=C57BL/6J; RA Xu P., Taylor S.; RL Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; 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 [5] RP FUNCTION IN PHOSPHORYLATION OF PKN1 AND PKN2, AND INTERACTION WITH PKN1 AND RP PKN2. RX PubMed=10792047; DOI=10.1073/pnas.090491897; RA Dong L.Q., Landa L.R., Wick M.J., Zhu L., Mukai H., Ono Y., Liu F.; RT "Phosphorylation of protein kinase N by phosphoinositide-dependent protein RT kinase-1 mediates insulin signals to the actin cytoskeleton."; RL Proc. Natl. Acad. Sci. U.S.A. 97:5089-5094(2000). RN [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-244, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic brain; RX PubMed=15345747; DOI=10.1074/mcp.m400085-mcp200; RA Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.; RT "Phosphoproteomic analysis of the developing mouse brain."; RL Mol. Cell. Proteomics 3:1093-1101(2004). RN [7] RP FUNCTION, AND INTERACTION WITH PPARG. RX PubMed=16150867; DOI=10.1210/me.2005-0197; RA Yin Y., Yuan H., Wang C., Pattabiraman N., Rao M., Pestell R.G., RA Glazer R.I.; RT "3-phosphoinositide-dependent protein kinase-1 activates the peroxisome RT proliferator-activated receptor-gamma and promotes adipocyte RT differentiation."; RL Mol. Endocrinol. 20:268-278(2006). RN [8] RP FUNCTION. RX PubMed=17599070; DOI=10.1038/sj.emboj.7601761; RA Kelly A.P., Finlay D.K., Hinton H.J., Clarke R.G., Fiorini E., Radtke F., RA Cantrell D.A.; RT "Notch-induced T cell development requires phosphoinositide-dependent RT kinase 1."; RL EMBO J. 26:3441-3450(2007). RN [9] 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 [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=17242355; DOI=10.1073/pnas.0609836104; RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.; RT "Large-scale phosphorylation analysis of mouse liver."; RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007). RN [11] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=19635472; DOI=10.1016/j.ydbio.2009.07.030; RA Westmoreland J.J., Wang Q., Bouzaffour M., Baker S.J., Sosa-Pineda B.; RT "Pdk1 activity controls proliferation, survival, and growth of developing RT pancreatic cells."; RL Dev. Biol. 334:285-298(2009). RN [12] RP PHOSPHORYLATION AT SER-504 AND SER-532 BY PKC/PRKCQ. RX PubMed=19047061; DOI=10.1074/jbc.m806336200; RA Wang C., Liu M., Riojas R.A., Xin X., Gao Z., Zeng R., Wu J., Dong L.Q., RA Liu F.; RT "Protein kinase C theta (PKCtheta)-dependent phosphorylation of PDK1 at RT Ser504 and Ser532 contributes to palmitate-induced insulin resistance."; RL J. Biol. Chem. 284:2038-2044(2009). RN [13] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=19429709; DOI=10.1073/pnas.0900064106; RA Ito K., Akazawa H., Tamagawa M., Furukawa K., Ogawa W., Yasuda N., Kudo Y., RA Liao C.H., Yamamoto R., Sato T., Molkentin J.D., Kasuga M., Noda T., RA Nakaya H., Komuro I.; RT "PDK1 coordinates survival pathways and beta-adrenergic response in the RT heart."; RL Proc. Natl. Acad. Sci. U.S.A. 106:8689-8694(2009). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-244, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, RC Pancreas, Spleen, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [15] RP FUNCTION. RX PubMed=21063107; DOI=10.1159/000322337; RA Shumilina E., Zemtsova I.M., Heise N., Schmid E., Eichenmueller M., RA Tyan L., Rexhepaj R., Lang F.; RT "Phosphoinositide-dependent kinase PDK1 in the regulation of Ca2+ entry RT into mast cells."; RL Cell. Physiol. Biochem. 26:699-706(2010). RN [16] RP FUNCTION. RX PubMed=20584979; DOI=10.1128/mcb.00069-10; RA Chaurasia B., Mauer J., Koch L., Goldau J., Kock A.S., Bruening J.C.; RT "Phosphoinositide-dependent kinase 1 provides negative feedback inhibition RT to Toll-like receptor-mediated NF-kappaB activation in macrophages."; RL Mol. Cell. Biol. 30:4354-4366(2010). RN [17] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-307, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic fibroblast; RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001; RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.; RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic RT pathways."; RL Mol. Cell 50:919-930(2013). 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. {ECO:0000269|PubMed:10792047, CC ECO:0000269|PubMed:16150867, ECO:0000269|PubMed:17371830, CC ECO:0000269|PubMed:17599070, ECO:0000269|PubMed:19429709, CC ECO:0000269|PubMed:19635472, ECO:0000269|PubMed:20584979, CC ECO:0000269|PubMed:21063107}. 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-376 and Tyr-379 residues. The 14-3-3 protein YWHAQ acts CC as a negative regulator by association with the residues surrounding CC the Ser-244 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-376 and Tyr-379 by INSR in response to CC insulin (By similarity). {ECO:0000250}. CC -!- SUBUNIT: Homodimer in its autoinhibited state. Active as monomer. CC Interacts with NPRL2, PAK1, PTK2B, GRB14, STRAP and IKKB. The Tyr-9 CC phosphorylated form interacts with SRC, RASA1 and CRK (via their SH2 CC domains). Interacts with SGK3 in a phosphorylation-dependent manner. CC The tyrosine-phosphorylated form interacts with PTPN6. The Ser-244 CC phosphorylated form interacts with YWHAH and YWHAQ. Binds INSR in CC response to insulin. Interacts (via PH domain) with SMAD3, SMAD4 and CC SMAD7. Interacts with PKN2; the interaction stimulates PDPK1 CC autophosphorylation, its PI(3,4,5)P3-dependent kinase activity toward CC 'Ser-473' of AKT1 but also activates its kinase activity toward PRKCD CC and PRKCZ (By similarity). Interacts with PKN1 (via C-terminus) and CC PPARG. {ECO:0000250, ECO:0000269|PubMed:10792047, CC ECO:0000269|PubMed:16150867}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17371830}. Nucleus CC {ECO:0000250}. Cell membrane {ECO:0000269|PubMed:17371830}; Peripheral CC membrane protein {ECO:0000269|PubMed:17371830}. Cell junction, focal CC adhesion {ECO:0000250}. Note=Tyrosine phosphorylation seems to occur CC only at the cell membrane. Translocates to the cell membrane following CC insulin stimulation by a mechanism that involves binding to GRB14 and CC INSR. SRC and HSP90 promote its localization to the cell membrane. Its CC nuclear localization is dependent on its association with PTPN6 and its CC phosphorylation at Ser-396. Restricted to the nucleus in neuronal cells CC while in non-neuronal cells it is found in the cytoplasm. The Ser-244 CC phosphorylated form is distributed along the perinuclear region in CC neuronal cells while in non-neuronal cells it is found in both the CC nucleus and the cytoplasm. IGF1 transiently increases phosphorylation CC at Ser-241 of neuronal PDPK1, resulting in its translocation to other CC cellular compartments. The tyrosine-phosphorylated form colocalizes CC with PTK2B in focal adhesions after angiotensin II stimulation (By CC similarity). {ECO:0000250}. CC -!- TISSUE SPECIFICITY: Highly expressed in heart, brain, liver and testis, CC also expressed in embryonic cells. 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 {ECO:0000250}. 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:0000250|UniProtKB:O15530}. CC -!- PTM: Phosphorylation on Ser-244 in the activation loop is required for CC full activity. PDPK1 itself can autophosphorylate Ser-244, 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-376 and Tyr-379 by INSR in response to CC insulin. Palmitate negatively regulates autophosphorylation at Ser-244 CC and palmitate-induced phosphorylation at Ser-532 and Ser-504 by CC PKC/PRKCQ negatively regulates its ability to phosphorylate PKB/AKT1. CC Phosphorylation at Thr-357 by MELK partially inhibits kinase activity, CC the inhibition is cooperatively enhanced by phosphorylation at Ser-397 CC and Ser-401 by MAP3K5 (By similarity). {ECO:0000250}. CC -!- PTM: Monoubiquitinated in the kinase domain, deubiquitinated by USP4. CC {ECO:0000250}. CC -!- DISRUPTION PHENOTYPE: Mice show severe pancreatic hypoplasia at birth CC and ensuing hyperglycemia at postnatal stages and die of heart failure CC by 11 weeks of age. {ECO:0000269|PubMed:19429709, CC ECO:0000269|PubMed:19635472}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr CC protein kinase family. PDPK1 subfamily. {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; AF086625; AAC67544.1; -; mRNA. DR EMBL; AF126294; AAD38505.1; -; mRNA. DR EMBL; AF079535; AAC96115.1; -; mRNA. DR EMBL; BC146001; AAI46002.1; -; mRNA. DR EMBL; BC146003; AAI46004.1; -; mRNA. DR CCDS; CCDS28474.1; -. DR RefSeq; NP_035192.2; NM_011062.4. DR AlphaFoldDB; Q9Z2A0; -. DR SMR; Q9Z2A0; -. DR BioGRID; 202099; 10. DR IntAct; Q9Z2A0; 18. DR STRING; 10090.ENSMUSP00000099991; -. DR GlyGen; Q9Z2A0; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9Z2A0; -. DR PhosphoSitePlus; Q9Z2A0; -. DR EPD; Q9Z2A0; -. DR jPOST; Q9Z2A0; -. DR MaxQB; Q9Z2A0; -. DR PaxDb; 10090-ENSMUSP00000099991; -. DR ProteomicsDB; 294051; -. DR Pumba; Q9Z2A0; -. DR Antibodypedia; 3794; 1207 antibodies from 47 providers. DR DNASU; 18607; -. DR Ensembl; ENSMUST00000102927.10; ENSMUSP00000099991.4; ENSMUSG00000024122.17. DR GeneID; 18607; -. DR KEGG; mmu:18607; -. DR UCSC; uc008auk.3; mouse. DR AGR; MGI:1338068; -. DR CTD; 5170; -. DR MGI; MGI:1338068; Pdpk1. DR VEuPathDB; HostDB:ENSMUSG00000024122; -. DR eggNOG; KOG0592; Eukaryota. DR GeneTree; ENSGT00940000155267; -. DR InParanoid; Q9Z2A0; -. DR OMA; GYPSIRA; -. DR OrthoDB; 208777at2759; -. DR PhylomeDB; Q9Z2A0; -. DR TreeFam; TF105423; -. DR BRENDA; 2.7.11.1; 3474. DR Reactome; R-MMU-114604; GPVI-mediated activation cascade. DR Reactome; R-MMU-1257604; PIP3 activates AKT signaling. DR Reactome; R-MMU-165158; Activation of AKT2. DR Reactome; R-MMU-202424; Downstream TCR signaling. DR Reactome; R-MMU-2730905; Role of LAT2/NTAL/LAB on calcium mobilization. DR Reactome; R-MMU-2871837; FCERI mediated NF-kB activation. DR Reactome; R-MMU-354192; Integrin signaling. DR Reactome; R-MMU-389357; CD28 dependent PI3K/Akt signaling. DR Reactome; R-MMU-392451; G beta:gamma signalling through PI3Kgamma. DR Reactome; R-MMU-5218920; VEGFR2 mediated vascular permeability. DR Reactome; R-MMU-5218921; VEGFR2 mediated cell proliferation. DR Reactome; R-MMU-5607764; CLEC7A (Dectin-1) signaling. DR Reactome; R-MMU-5625740; RHO GTPases activate PKNs. DR Reactome; R-MMU-6804757; Regulation of TP53 Degradation. DR Reactome; R-MMU-9634635; Estrogen-stimulated signaling through PRKCZ. DR BioGRID-ORCS; 18607; 11 hits in 83 CRISPR screens. DR ChiTaRS; Pdpk1; mouse. DR PRO; PR:Q9Z2A0; -. DR Proteomes; UP000000589; Chromosome 17. DR RNAct; Q9Z2A0; Protein. DR Bgee; ENSMUSG00000024122; Expressed in rostral migratory stream and 271 other cell types or tissues. DR ExpressionAtlas; Q9Z2A0; baseline and differential. DR GO; GO:0042995; C:cell projection; ISO:MGI. DR GO; GO:0005737; C:cytoplasm; IDA:MGI. DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:MGI. DR GO; GO:0005829; C:cytosol; ISO:MGI. DR GO; GO:0005925; C:focal adhesion; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0043204; C:perikaryon; ISO:MGI. DR GO; GO:0005886; C:plasma membrane; ISO:MGI. DR GO; GO:0014069; C:postsynaptic density; IDA:MGI. DR GO; GO:0004676; F:3-phosphoinositide-dependent protein kinase activity; IDA:MGI. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0005158; F:insulin receptor binding; ISO:MGI. DR GO; GO:0016004; F:phospholipase activator activity; ISO:MGI. DR GO; GO:0043274; F:phospholipase binding; ISO:MGI. DR GO; GO:0019901; F:protein kinase binding; ISO:MGI. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISO:MGI. DR GO; GO:0019722; P:calcium-mediated signaling; IEA:Ensembl. DR GO; GO:0016477; P:cell migration; IEA:Ensembl. DR GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; IEA:Ensembl. DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IEA:Ensembl. DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; IEA:Ensembl. DR GO; GO:0048041; P:focal adhesion assembly; ISO:MGI. DR GO; GO:0006972; P:hyperosmotic response; IDA:MGI. DR GO; GO:0008286; P:insulin receptor signaling pathway; IDA:MGI. DR GO; GO:0048009; P:insulin-like growth factor receptor signaling pathway; IDA:MGI. DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central. DR GO; GO:0010667; P:negative regulation of cardiac muscle cell apoptotic process; IMP:UniProtKB. DR GO; GO:2000352; P:negative regulation of endothelial cell apoptotic process; IEA:Ensembl. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISO:MGI. DR GO; GO:0034122; P:negative regulation of toll-like receptor signaling pathway; IMP:UniProtKB. DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IEA:Ensembl. DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; IEA:Ensembl. DR GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; IEA:Ensembl. DR GO; GO:0051281; P:positive regulation of release of sequestered calcium ion into cytosol; IEA:Ensembl. DR GO; GO:1903672; P:positive regulation of sprouting angiogenesis; IEA:Ensembl. DR GO; GO:1905564; P:positive regulation of vascular endothelial cell proliferation; IEA:Ensembl. DR GO; GO:0043122; P:regulation of canonical NF-kappaB signal transduction; IEA:Ensembl. DR GO; GO:0010594; P:regulation of endothelial cell migration; IMP:UniProtKB. DR GO; GO:0043304; P:regulation of mast cell degranulation; IMP:UniProtKB. DR GO; GO:0007165; P:signal transduction; TAS:MGI. DR GO; GO:0003323; P:type B pancreatic cell development; IMP:UniProtKB. 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; Q9Z2A0; MM. PE 1: Evidence at protein level; KW Acetylation; ATP-binding; Cell junction; Cell membrane; Cytoplasm; Kinase; KW Membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; KW Serine/threonine-protein kinase; Transcription; Transcription regulation; KW Transferase; Ubl conjugation. FT CHAIN 1..559 FT /note="3-phosphoinositide-dependent protein kinase 1" FT /id="PRO_0000086501" FT DOMAIN 85..345 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT DOMAIN 462..553 FT /note="PH" FT REGION 25..83 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 116..160 FT /note="PIF-pocket" FT /evidence="ECO:0000250|UniProtKB:O15530" FT COMPBIAS 25..69 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 208 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10027" FT BINDING 95..97 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:O15530" FT BINDING 114 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:O15530" FT BINDING 163..165 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:O15530" FT BINDING 169 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:O15530" FT BINDING 212 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:O15530" FT BINDING 226 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:O15530" FT MOD_RES 9 FT /note="Phosphotyrosine; by SRC and INSR" FT /evidence="ECO:0000250|UniProtKB:O15530" FT MOD_RES 25 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O15530" FT MOD_RES 244 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:15345747, FT ECO:0007744|PubMed:21183079" FT MOD_RES 307 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:23806337" FT MOD_RES 357 FT /note="Phosphothreonine; by MELK" FT /evidence="ECO:0000250|UniProtKB:O15530" FT MOD_RES 376 FT /note="Phosphotyrosine; by SRC and INSR" FT /evidence="ECO:0000250|UniProtKB:O15530" FT MOD_RES 379 FT /note="Phosphotyrosine; by SRC and INSR" FT /evidence="ECO:0000250|UniProtKB:O15530" FT MOD_RES 396 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O15530" FT MOD_RES 397 FT /note="Phosphoserine; by MAP3K5" FT /evidence="ECO:0000250|UniProtKB:O15530" FT MOD_RES 399 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O15530" FT MOD_RES 401 FT /note="Phosphoserine; by MAP3K5" FT /evidence="ECO:0000250|UniProtKB:O15530" FT MOD_RES 413 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O15530" FT MOD_RES 504 FT /note="Phosphoserine; by PKC/PRKCQ" FT /evidence="ECO:0000269|PubMed:19047061" FT MOD_RES 516 FT /note="Phosphothreonine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:O15530" FT MOD_RES 532 FT /note="Phosphoserine; by PKC/PRKCQ" FT /evidence="ECO:0000269|PubMed:19047061" FT CONFLICT 84 FT /note="D -> N (in Ref. 1; AAC67544)" FT /evidence="ECO:0000305" FT CONFLICT 248 FT /note="T -> P (in Ref. 3; AAC96115)" FT /evidence="ECO:0000305" FT CONFLICT 285 FT /note="F -> S (in Ref. 3; AAC96115)" FT /evidence="ECO:0000305" FT CONFLICT 546 FT /note="W -> R (in Ref. 3; AAC96115)" FT /evidence="ECO:0000305" SQ SEQUENCE 559 AA; 63759 MW; F2A617A27460FAC9 CRC64; MARTTSQLYD AVPIQSSVVL CSCPSPSMVR SQTEPGSSPG IPSGVSRQGS TMDGTTAEAR PSTNPLQQHP AQLPPQPRKK RPEDFKFGKI LGEGSFSTVV LARELATSRE YAIKILEKRH IIKENKVPYV TRERDVMSRL DHPFFVKLYF TFQDDEKLYF GLSYAKNGEL LKYIRKIGSF DETCTRFYTA EIVSALEYLH GKGIIHRDLK PENILLNEDM HIQITDFGTA KVLSPESKQA RANSFVGTAQ YVSPELLTEK SACKSSDLWA LGCIIYQLVA GLPPFRAGNE YLIFQKIIKL EYHFPEKFFP KARDLVEKLL VLDATKRLGC EEMEGYGPLK AHPFFETITW ENLHQQTPPK LTAYLPAMSE DDEDCYGNYD NLLSQFGFMQ VSSSSSSHSL STVETSLPQR SGSNIEQYIH DLDTNSFELD LQFSEDEKRL LLEKQAGGNP WHQFVENNLI LKMGPVDKRK GLFARRRQLL LTEGPHLYYV DPVNKVLKGE IPWSQELRPE AKNFKTFFVH TPNRTYYLMD PSGNAHKWCR KIQEVWRQQY QSNPDAAVQ //