PDPK1_RAT
ID PDPK1_RAT Reviewed; 559 AA.
AC O55173; G3V9W3;
DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot.
DT 11-JUL-2012, sequence version 2.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=3-phosphoinositide-dependent protein kinase 1;
DE EC=2.7.11.1;
DE AltName: Full=Protein kinase B kinase;
DE Short=PkB kinase;
GN Name=Pdpk1; Synonyms=Pdk1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15632090; DOI=10.1101/gr.2889405;
RA Florea L., Di Francesco V., Miller J., Turner R., Yao A., Harris M.,
RA Walenz B., Mobarry C., Merkulov G.V., Charlab R., Dew I., Deng Z.,
RA Istrail S., Li P., Sutton G.;
RT "Gene and alternative splicing annotation with AIR.";
RL Genome Res. 15:54-66(2005).
RN [4]
RP FUNCTION IN PHOSPHORYLATION OF PRKCD AND PRKCZ, AUTOPHOSPHORYLATION, AND
RP INTERACTION WITH PRKCD AND PRKCZ.
RX PubMed=11781095; DOI=10.1021/bi010719z;
RA Hodgkinson C.P., Sale G.J.;
RT "Regulation of both PDK1 and the phosphorylation of PKC-zeta and -delta by
RT a C-terminal PRK2 fragment.";
RL Biochemistry 41:561-569(2002).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-244, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(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 (By similarity). {ECO:0000250,
CC ECO:0000269|PubMed:11781095}.
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, 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-244 phosphorylated form interacts with
CC YWHAH and YWHAQ. Binds INSR in response to insulin. Interacts (via PH
CC domain) with SMAD3, SMAD4 and SMAD7 (By similarity). Interacts with
CC PKN2; the interaction stimulates PDPK1 autophosphorylation, its
CC PI(3,4,5)P3-dependent kinase activity toward 'Ser-473' of AKT1 but also
CC activates its kinase activity toward PRKCD and PRKCZ. {ECO:0000250,
CC ECO:0000269|PubMed:11781095}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC Cell membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}.
CC Cell junction, focal adhesion {ECO:0000250}. 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-244 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-244 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 (By similarity).
CC {ECO:0000250}.
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. Tyr-9 phosphorylation is critical
CC for stabilization of both PDPK1 and the PDPK1/SRC complex via HSP90-
CC mediated protection of PDPK1 degradation. Angiotensin II stimulates the
CC tyrosine phosphorylation of PDPK1 in vascular smooth muscle in a
CC calcium- and SRC-dependent manner. Phosphorylated on Tyr-9, Tyr-376 and
CC Tyr-379 by INSR in response to insulin. Palmitate negatively regulates
CC autophosphorylation at Ser-244 and palmitate-induced phosphorylation at
CC Ser-532 and Ser-504 by PKC/PRKCQ negatively regulates its ability to
CC phosphorylate PKB/AKT1. Phosphorylation at Thr-357 by MELK partially
CC inhibits kinase activity, the inhibition is cooperatively enhanced by
CC phosphorylation at Ser-397 and Ser-401 by MAP3K5 (By similarity).
CC {ECO:0000250}.
CC -!- PTM: Monoubiquitinated in the kinase domain, deubiquitinated by USP4.
CC {ECO:0000250}.
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; Y15748; CAA75758.1; -; mRNA.
DR EMBL; CH473948; EDM03805.1; -; Genomic_DNA.
DR RefSeq; NP_112343.1; NM_031081.1.
DR AlphaFoldDB; O55173; -.
DR SMR; O55173; -.
DR CORUM; O55173; -.
DR STRING; 10116.ENSRNOP00000061683; -.
DR iPTMnet; O55173; -.
DR PhosphoSitePlus; O55173; -.
DR jPOST; O55173; -.
DR PaxDb; O55173; -.
DR PRIDE; O55173; -.
DR Ensembl; ENSRNOT00000067660; ENSRNOP00000061683; ENSRNOG00000006136.
DR GeneID; 81745; -.
DR KEGG; rno:81745; -.
DR UCSC; RGD:620307; rat.
DR CTD; 5170; -.
DR RGD; 620307; Pdpk1.
DR eggNOG; KOG0592; Eukaryota.
DR GeneTree; ENSGT00940000155267; -.
DR HOGENOM; CLU_000288_63_9_1; -.
DR InParanoid; O55173; -.
DR OMA; GYPSIRA; -.
DR OrthoDB; 1157543at2759; -.
DR TreeFam; TF105423; -.
DR BRENDA; 2.7.11.1; 5301.
DR Reactome; R-RNO-114604; GPVI-mediated activation cascade.
DR Reactome; R-RNO-1257604; PIP3 activates AKT signaling.
DR Reactome; R-RNO-165158; Activation of AKT2.
DR Reactome; R-RNO-202424; Downstream TCR signaling.
DR Reactome; R-RNO-2730905; Role of LAT2/NTAL/LAB on calcium mobilization.
DR Reactome; R-RNO-2871837; FCERI mediated NF-kB activation.
DR Reactome; R-RNO-354192; Integrin signaling.
DR Reactome; R-RNO-389357; CD28 dependent PI3K/Akt signaling.
DR Reactome; R-RNO-392451; G beta:gamma signalling through PI3Kgamma.
DR Reactome; R-RNO-5218920; VEGFR2 mediated vascular permeability.
DR Reactome; R-RNO-5218921; VEGFR2 mediated cell proliferation.
DR Reactome; R-RNO-5607764; CLEC7A (Dectin-1) signaling.
DR Reactome; R-RNO-5625740; RHO GTPases activate PKNs.
DR Reactome; R-RNO-6804757; Regulation of TP53 Degradation.
DR Reactome; R-RNO-9634635; Estrogen-stimulated signaling through PRKCZ.
DR PRO; PR:O55173; -.
DR Proteomes; UP000002494; Chromosome 10.
DR Proteomes; UP000234681; Chromosome 10.
DR Bgee; ENSRNOG00000006136; Expressed in testis and 19 other tissues.
DR Genevisible; O55173; RN.
DR GO; GO:0042995; C:cell projection; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
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; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0014069; C:postsynaptic density; ISO:RGD.
DR GO; GO:0004676; F:3-phosphoinositide-dependent protein kinase activity; IDA:RGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005158; F:insulin receptor binding; IDA:RGD.
DR GO; GO:0016004; F:phospholipase activator activity; ISO:RGD.
DR GO; GO:0043274; F:phospholipase binding; ISO:RGD.
DR GO; GO:0019901; F:protein kinase binding; IDA:RGD.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISO:RGD.
DR GO; GO:0032148; P:activation of protein kinase B activity; ISO:RGD.
DR GO; GO:0019722; P:calcium-mediated signaling; ISO:RGD.
DR GO; GO:0016477; P:cell migration; ISO:RGD.
DR GO; GO:1990416; P:cellular response to brain-derived neurotrophic factor stimulus; IEP:RGD.
DR GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; ISO:RGD.
DR GO; GO:0032869; P:cellular response to insulin stimulus; ISO:RGD.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; ISO:RGD.
DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0048041; P:focal adhesion assembly; IMP:RGD.
DR GO; GO:0006972; P:hyperosmotic response; ISO:RGD.
DR GO; GO:0035556; P:intracellular signal transduction; ISO:RGD.
DR GO; GO:0010667; P:negative regulation of cardiac muscle cell apoptotic process; ISO:RGD.
DR GO; GO:2000352; P:negative regulation of endothelial cell apoptotic process; ISO:RGD.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:RGD.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; ISO:RGD.
DR GO; GO:0034122; P:negative regulation of toll-like receptor signaling pathway; ISO:RGD.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; ISO:RGD.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; ISO:RGD.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISO:RGD.
DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; ISO:RGD.
DR GO; GO:0010518; P:positive regulation of phospholipase activity; ISO:RGD.
DR GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; ISO:RGD.
DR GO; GO:0051281; P:positive regulation of release of sequestered calcium ion into cytosol; ISO:RGD.
DR GO; GO:1903672; P:positive regulation of sprouting angiogenesis; ISO:RGD.
DR GO; GO:1905564; P:positive regulation of vascular endothelial cell proliferation; ISO:RGD.
DR GO; GO:0006468; P:protein phosphorylation; ISO:RGD.
DR GO; GO:0010594; P:regulation of endothelial cell migration; ISO:RGD.
DR GO; GO:0043122; P:regulation of I-kappaB kinase/NF-kappaB signaling; ISO:RGD.
DR GO; GO:0043304; P:regulation of mast cell degranulation; ISO:RGD.
DR GO; GO:0003323; P:type B pancreatic cell development; ISO:RGD.
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_0000086502"
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:22673903"
FT MOD_RES 307
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z2A0"
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:0000250|UniProtKB:Q9Z2A0"
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:0000250|UniProtKB:Q9Z2A0"
FT CONFLICT 401
FT /note="S -> C (in Ref. 1; CAA75758)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 559 AA; 63593 MW; 4D06A17F769B800F CRC64;
MARTTSQLYD AVPIQSSVVL CSCPSPSMVR SQTEPSSSPG IPSGVSRQGS TMDGTTAEAR
PSTNPLQQHP AQLPPQPRKK RPEDFKFGKI LGEGSFSTVV LARELATSRE YAIKILEKRH
IIKENKVPYV TRERDVMSRL DHPFFVKLYF TFQDDEKLYF GLSYAKNGEL LKYIRKIGSF
DETCTRFYTA EIVSALEYLH GKGIIHRDLK PENILLNEDM HIQITDFGTA KVLSPDSKQA
RANSFVGTAQ YVSPELLTEK SACKSSDLWA LGCIIYQLVA GLPPFRAGNE YLIFQKIIKL
EYDFPEKFFP KARDLVEKLL VLDATKRLGC EEMEGYGPLK AHPFFESITW ENLHQQTPPK
LTAYLPAMSE DDEDCYGNYD NLLSQFGCMQ VSSSSSSHSL SAVDASLPQR SGSNIEQYIH
DLDTNSFELD LQFSEDEKRL LLEKQAGGNP WHQFVENNLI LKMGPVDKRK GLFARRRQLL
LTEGPHLYYV DPVNKVLKGE IPWSQELRPE AKNFKTFFVH TPNRTYYLMD PSGNAHKWCR
KIQEVWRQQY QSSPDAAVQ
