PDPK1_MOUSE
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 03-AUG-2022, entry version 192.
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, Pancreas,
RC 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}.
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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 iPTMnet; Q9Z2A0; -.
DR PhosphoSitePlus; Q9Z2A0; -.
DR EPD; Q9Z2A0; -.
DR jPOST; Q9Z2A0; -.
DR MaxQB; Q9Z2A0; -.
DR PaxDb; Q9Z2A0; -.
DR PRIDE; Q9Z2A0; -.
DR ProteomicsDB; 294051; -.
DR Antibodypedia; 3794; 993 antibodies from 47 providers.
DR DNASU; 18607; -.
DR Ensembl; ENSMUST00000102927; ENSMUSP00000099991; ENSMUSG00000024122.
DR GeneID; 18607; -.
DR KEGG; mmu:18607; -.
DR UCSC; uc008auk.3; mouse.
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; 1157543at2759; -.
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 78 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 267 other tissues.
DR ExpressionAtlas; Q9Z2A0; baseline and differential.
DR Genevisible; Q9Z2A0; MM.
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:0032148; P:activation of protein kinase B activity; IEA:Ensembl.
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:0032869; P:cellular response to insulin 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: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:0006469; P:negative regulation of protein kinase activity; IEA:Ensembl.
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:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IEA:Ensembl.
DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; IEA:Ensembl.
DR GO; GO:0010518; P:positive regulation of phospholipase activity; 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:0010594; P:regulation of endothelial cell migration; IMP:UniProtKB.
DR GO; GO:0043122; P:regulation of I-kappaB kinase/NF-kappaB signaling; IEA:Ensembl.
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; -; 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 Pfam; PF14593; PH_3; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 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 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
