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Protein

3-phosphoinositide-dependent protein kinase 1

Gene

PDPK1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Serine/threonine kinase which acts as a master kinase, phosphorylating and activating a subgroup of the AGC family of protein kinases. Its targets include: protein kinase B (PKB/AKT1, PKB/AKT2, PKB/AKT3), p70 ribosomal protein S6 kinase (RPS6KB1), p90 ribosomal protein S6 kinase (RPS6KA1, RPS6KA2 and RPS6KA3), cyclic AMP-dependent protein kinase (PRKACA), protein kinase C (PRKCD and PRKCZ), serum and glucocorticoid-inducible kinase (SGK1, SGK2 and SGK3), p21-activated kinase-1 (PAK1), protein kinase PKN (PKN1 and PKN2). Plays a central role in the transduction of signals from insulin by providing the activating phosphorylation to PKB/AKT1, thus propagating the signal to downstream targets controlling cell proliferation and survival, as well as glucose and amino acid uptake and storage. Negatively regulates the TGF-beta-induced signaling by: modulating the association of SMAD3 and SMAD7 with TGF-beta receptor, phosphorylating SMAD2, SMAD3, SMAD4 and SMAD7, preventing the nuclear translocation of SMAD3 and SMAD4 and the translocation of SMAD7 from the nucleus to the cytoplasm in response to TGF-beta. Activates PPARG transcriptional activity and promotes adipocyte differentiation. Activates the NF-kappa-B pathway via phosphorylation of IKKB. The tyrosine phosphorylated form is crucial for the regulation of focal adhesions by angiotensin II. Controls proliferation, survival, and growth of developing pancreatic cells. Participates in the regulation of Ca2+ entry and Ca2+-activated K+ channels of mast cells. Essential for the motility of vascular endothelial cells (ECs) and is involved in the regulation of their chemotaxis. Plays a critical role in cardiac homeostasis by serving as a dual effector for cell survival and beta-adrenergic response. Plays an important role during thymocyte development by regulating the expression of key nutrient receptors on the surface of pre-T cells and mediating Notch-induced cell growth and proliferative responses. Provides negative feedback inhibition to toll-like receptor-mediated NF-kappa-B activation in macrophages. Isoform 3 is catalytically inactive.15 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

Homodimerization regulates its activity by maintaining the kinase in an autoinhibitory conformation. NPRL2 down-regulates its activity by interfering with tyrosine phosphorylation at the Tyr-9, Tyr-373 and Tyr-376 residues. The 14-3-3 protein YWHAQ acts as a negative regulator by association with the residues surrounding the Ser-241 residue. STRAP positively regulates its activity by enhancing its autophosphorylation and by stimulating its dissociation from YWHAQ. SMAD2, SMAD3, SMAD4 and SMAD7 also positively regulate its activity by stimulating its dissociation from YWHAQ. Activated by phosphorylation on Tyr-9, Tyr-373 and Tyr-376 by INSR in response to insulin.4 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei111 – 1111ATP3 Publications
Binding sitei166 – 1661ATP3 Publications
Active sitei205 – 2051Proton acceptorPROSITE-ProRule annotation
Binding sitei209 – 2091ATP; via carbonyl oxygen1 Publication
Binding sitei223 – 2231ATP3 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi92 – 943ATP3 Publications
Nucleotide bindingi160 – 1623ATP3 Publications

GO - Molecular functioni

  • 3-phosphoinositide-dependent protein kinase activity Source: BHF-UCL
  • ATP binding Source: UniProtKB-KW
  • kinase activity Source: Reactome
  • phospholipase activator activity Source: BHF-UCL
  • phospholipase binding Source: BHF-UCL
  • protein serine/threonine kinase activity Source: BHF-UCL

GO - Biological processi

  • actin cytoskeleton organization Source: ProtInc
  • activation of protein kinase B activity Source: BHF-UCL
  • blood coagulation Source: Reactome
  • calcium-mediated signaling Source: BHF-UCL
  • cell migration Source: BHF-UCL
  • cellular response to epidermal growth factor stimulus Source: BHF-UCL
  • cellular response to insulin stimulus Source: BHF-UCL
  • epidermal growth factor receptor signaling pathway Source: BHF-UCL
  • extrinsic apoptotic signaling pathway Source: UniProtKB
  • Fc-epsilon receptor signaling pathway Source: Reactome
  • fibroblast growth factor receptor signaling pathway Source: Reactome
  • focal adhesion assembly Source: Ensembl
  • hyperosmotic response Source: Ensembl
  • innate immune response Source: Reactome
  • insulin receptor signaling pathway Source: Reactome
  • intracellular signal transduction Source: MGI
  • negative regulation of cardiac muscle cell apoptotic process Source: Ensembl
  • negative regulation of protein kinase activity Source: BHF-UCL
  • negative regulation of toll-like receptor signaling pathway Source: Ensembl
  • negative regulation of transforming growth factor beta receptor signaling pathway Source: UniProtKB
  • neurotrophin TRK receptor signaling pathway Source: Reactome
  • peptidyl-threonine phosphorylation Source: BHF-UCL
  • phosphatidylinositol-mediated signaling Source: Reactome
  • platelet activation Source: Reactome
  • positive regulation of establishment of protein localization to plasma membrane Source: BHF-UCL
  • positive regulation of phospholipase activity Source: BHF-UCL
  • positive regulation of release of sequestered calcium ion into cytosol Source: BHF-UCL
  • protein autophosphorylation Source: UniProtKB
  • protein phosphorylation Source: UniProtKB
  • regulation of endothelial cell migration Source: Ensembl
  • regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • regulation of mast cell degranulation Source: Ensembl
  • regulation of transcription, DNA-templated Source: UniProtKB-KW
  • small GTPase mediated signal transduction Source: Reactome
  • stimulatory C-type lectin receptor signaling pathway Source: Reactome
  • synaptic transmission Source: Reactome
  • T cell costimulation Source: Reactome
  • T cell receptor signaling pathway Source: Reactome
  • transcription, DNA-templated Source: UniProtKB-KW
  • type B pancreatic cell development Source: Ensembl
  • vascular endothelial growth factor receptor signaling pathway Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Activator, Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.1. 2681.
ReactomeiREACT_12555. Downstream TCR signaling.
REACT_15523. Integrin alphaIIb beta3 signaling.
REACT_163769. Role of LAT2/NTAL/LAB on calcium mobilization.
REACT_163994. FCERI mediated NF-kB activation.
REACT_1695. GPVI-mediated activation cascade.
REACT_188323. CLEC7A (Dectin-1) signaling.
REACT_19290. G beta:gamma signalling through PI3Kgamma.
REACT_19358. CD28 dependent PI3K/Akt signaling.
REACT_19405. CTLA4 inhibitory signaling.
REACT_20510. RSK activation.
REACT_263991. VEGFR2 mediated vascular permeability.
REACT_264273. VEGFR2 mediated cell proliferation.
REACT_355468. Constitutive Signaling by AKT1 E17K in Cancer.
REACT_355542. RHO GTPases activate PKNs.
REACT_75829. PIP3 activates AKT signaling.
REACT_790. Activation of PKB.
SignaLinkiO15530.

Names & Taxonomyi

Protein namesi
Recommended name:
3-phosphoinositide-dependent protein kinase 1 (EC:2.7.11.1)
Short name:
hPDK1
Gene namesi
Name:PDPK1
Synonyms:PDK1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:8816. PDPK1.

Subcellular locationi

  • Cytoplasm
  • Nucleus
  • Cell membrane; Peripheral membrane protein
  • Cell junctionfocal adhesion

  • Note: Tyrosine phosphorylation seems to occur only at the cell membrane. Translocates to the cell membrane following insulin stimulation by a mechanism that involves binding to GRB14 and INSR. SRC and HSP90 promote its localization to the cell membrane. Its nuclear localization is dependent on its association with PTPN6 and its phosphorylation at Ser-396. Restricted to the nucleus in neuronal cells while in non-neuronal cells it is found in the cytoplasm. The Ser-241 phosphorylated form is distributed along the perinuclear region in neuronal cells while in non-neuronal cells it is found in both the nucleus and the cytoplasm. IGF1 transiently increases phosphorylation at Ser-241 of neuronal PDPK1, resulting in its translocation to other cellular compartments. The tyrosine-phosphorylated form colocalizes with PTK2B in focal adhesions after angiotensin II stimulation.

GO - Cellular componenti

  • cell projection Source: BHF-UCL
  • cytoplasm Source: UniProtKB
  • cytoplasmic membrane-bounded vesicle Source: Ensembl
  • cytosol Source: Reactome
  • focal adhesion Source: UniProtKB-SubCell
  • nucleoplasm Source: Reactome
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi9 – 91Y → F: Slight reduction in pervanadate-stimulated tyrosine phosphorylation. 1 Publication
Mutagenesisi25 – 251S → A: No effect. 1 Publication
Mutagenesisi241 – 2411S → A: No activation. 1 Publication
Mutagenesisi277 – 2771A → V: 3-fold increase in kinase activity. 1 Publication
Mutagenesisi354 – 3541T → A: Abolishes phosphorylation by MELK. 1 Publication
Mutagenesisi373 – 3731Y → F: Reduction in basal activity. 1 Publication
Mutagenesisi376 – 3761Y → F: Reduction in basal activity. 1 Publication
Mutagenesisi393 – 3931S → A: No effect. 1 Publication
Mutagenesisi394 – 3941S → A: Abolishes phosphorylation by MAP3K5; when associated with A-398. 1 Publication
Mutagenesisi396 – 3961S → A: No effect. 1 Publication
Mutagenesisi398 – 3981S → A: Abolishes phosphorylation by MAP3K5; when associated with A-394. 1 Publication
Mutagenesisi410 – 4101S → A: No effect. 1 Publication
Mutagenesisi474 – 4741R → A: No PDGF-dependent translocation to the membrane. 1 Publication
Mutagenesisi513 – 5131T → E: Enhanced kinase activity towards PKB. 1 Publication

Organism-specific databases

PharmGKBiPA33160.

Chemistry

DrugBankiDB00482. Celecoxib.

Polymorphism and mutation databases

BioMutaiPDPK1.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 5565563-phosphoinositide-dependent protein kinase 1PRO_0000086500Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei9 – 91Phosphotyrosine; by SRC and INSR3 Publications
Modified residuei25 – 251Phosphoserine1 Publication
Modified residuei241 – 2411Phosphoserine; by autocatalysis5 Publications
Modified residuei304 – 3041N6-acetyllysineBy similarity
Modified residuei354 – 3541Phosphothreonine; by MELK1 Publication
Modified residuei373 – 3731Phosphotyrosine; by SRC and INSR3 Publications
Modified residuei376 – 3761Phosphotyrosine; by SRC and INSR3 Publications
Modified residuei393 – 3931Phosphoserine1 Publication
Modified residuei394 – 3941Phosphoserine; by MAP3K51 Publication
Modified residuei396 – 3961Phosphoserine2 Publications
Modified residuei398 – 3981Phosphoserine; by MAP3K51 Publication
Modified residuei410 – 4101Phosphoserine1 Publication
Modified residuei501 – 5011Phosphoserine; by PKC/PRKCQBy similarity
Modified residuei513 – 5131Phosphothreonine; by autocatalysis1 Publication
Modified residuei529 – 5291Phosphoserine; by PKC/PRKCQBy similarity

Post-translational modificationi

Phosphorylation on Ser-241 in the activation loop is required for full activity. PDPK1 itself can autophosphorylate Ser-241, leading to its own activation. Autophosphorylation is inhibited by the apoptotic C-terminus cleavage product of PKN2 (By similarity). Tyr-9 phosphorylation is critical for stabilization of both PDPK1 and the PDPK1/SRC complex via HSP90-mediated protection of PDPK1 degradation. Angiotensin II stimulates the tyrosine phosphorylation of PDPK1 in vascular smooth muscle in a calcium- and SRC-dependent manner. Phosphorylated on Tyr-9, Tyr-373 and Tyr-376 by INSR in response to insulin. Palmitate negatively regulates autophosphorylation at Ser-241 and palmitate-induced phosphorylation at Ser-529 and Ser-501 by PKC/PRKCQ negatively regulates its ability to phosphorylate PKB/AKT1. Phosphorylation at Thr-354 by MELK partially inhibits kinase activity, the inhibition is cooperatively enhanced by phosphorylation at Ser-394 and Ser-398 by MAP3K5.By similarity8 Publications
Autophosphorylated; autophosphorylation is inhibited by the apoptotic C-terminus cleavage product of PKN2.By similarity
Monoubiquitinated in the kinase domain, deubiquitinated by USP4.

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiO15530.
PaxDbiO15530.
PRIDEiO15530.

PTM databases

PhosphoSiteiO15530.

Expressioni

Tissue specificityi

Appears to be expressed ubiquitously. The Tyr-9 phosphorylated form is markedly increased in diseased tissue compared with normal tissue from lung, liver, colon and breast.1 Publication

Inductioni

Stimulated by insulin, and the oxidants hydrogen peroxide and peroxovanadate.

Gene expression databases

BgeeiO15530.
CleanExiHS_PDK1.
HS_PDPK1.
ExpressionAtlasiO15530. baseline and differential.
GenevisibleiO15530. HS.

Organism-specific databases

HPAiCAB004272.
HPA035199.

Interactioni

Subunit structurei

Homodimer in its autoinhibited state. Active as monomer. Interacts with NPRL2, PPARG, PAK1, PTK2B, GRB14, PKN1 (via C-terminus), STRAP and IKKB. The Tyr-9 phosphorylated form interacts with SRC, RASA1 and CRK (via their SH2 domains). Interacts with SGK3 in a phosphorylation-dependent manner. The tyrosine-phosphorylated form interacts with PTPN6. The Ser-241 phosphorylated form interacts with YWHAH and YWHAQ. Binds INSR in response to insulin. Interacts (via PH domain) with SMAD3, SMAD4 and SMAD7. Interacts with PKN2; the interaction stimulates PDPK1 autophosphorylation, its PI(3,4,5)P3-dependent kinase activity toward 'Ser-473' of AKT1 but also activates its kinase activity toward PRKCD and PRKCZ.14 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
AKT1P317493EBI-717097,EBI-296087
PPP2R2BQ000058EBI-717097,EBI-1052159
ZDHHC17Q8IUH53EBI-9087775,EBI-524753

Protein-protein interaction databases

BioGridi111196. 52 interactions.
DIPiDIP-38372N.
IntActiO15530. 49 interactions.
MINTiMINT-1371493.
STRINGi9606.ENSP00000344220.

Structurei

Secondary structure

1
556
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi79 – 813Combined sources
Beta strandi82 – 909Combined sources
Beta strandi95 – 1017Combined sources
Turni102 – 1043Combined sources
Beta strandi107 – 1159Combined sources
Helixi120 – 1223Combined sources
Helixi125 – 13511Combined sources
Beta strandi145 – 1506Combined sources
Beta strandi152 – 1598Combined sources
Beta strandi163 – 1664Combined sources
Helixi167 – 1748Combined sources
Helixi179 – 19820Combined sources
Helixi208 – 2103Combined sources
Beta strandi211 – 2133Combined sources
Beta strandi219 – 2213Combined sources
Helixi224 – 2263Combined sources
Turni232 – 2354Combined sources
Beta strandi238 – 2403Combined sources
Helixi246 – 2483Combined sources
Helixi251 – 2566Combined sources
Helixi261 – 27717Combined sources
Helixi287 – 29610Combined sources
Beta strandi303 – 3053Combined sources
Helixi307 – 31610Combined sources
Helixi321 – 3233Combined sources
Helixi328 – 3303Combined sources
Helixi333 – 3375Combined sources
Helixi340 – 3423Combined sources
Helixi347 – 3493Combined sources
Helixi350 – 3523Combined sources
Helixi412 – 4154Combined sources
Beta strandi416 – 4205Combined sources
Beta strandi423 – 4264Combined sources
Helixi432 – 44514Combined sources
Helixi449 – 4513Combined sources
Turni452 – 4543Combined sources
Beta strandi457 – 46711Combined sources
Beta strandi470 – 47910Combined sources
Turni480 – 4823Combined sources
Beta strandi483 – 4886Combined sources
Turni489 – 4924Combined sources
Beta strandi493 – 4986Combined sources
Beta strandi505 – 51814Combined sources
Beta strandi521 – 5266Combined sources
Helixi532 – 54716Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1H1WX-ray2.00A71-359[»]
1OKYX-ray2.30A51-360[»]
1OKZX-ray2.51A51-360[»]
1UU3X-ray1.70A51-360[»]
1UU7X-ray1.90A51-360[»]
1UU8X-ray2.50A51-360[»]
1UU9X-ray1.95A72-357[»]
1UVRX-ray2.81A71-359[»]
1W1DX-ray1.50A409-556[»]
1W1GX-ray1.45A409-556[»]
1W1HX-ray1.45A/B/C/D409-556[»]
1Z5MX-ray2.17A74-359[»]
2BIYX-ray1.95A51-360[»]
2PE0X-ray2.35A74-359[»]
2PE1X-ray2.14A74-359[»]
2PE2X-ray2.13A74-359[»]
2R7BX-ray2.70A48-359[»]
2VKIX-ray1.80A409-556[»]
2XCHX-ray2.00A51-359[»]
2XCKX-ray2.30A51-359[»]
3H9OX-ray2.30A51-359[»]
3HRCX-ray1.91A50-359[»]
3HRFX-ray1.90A50-359[»]
3IONX-ray2.40A48-359[»]
3IOPX-ray2.20A48-359[»]
3NAXX-ray1.75A66-362[»]
3NAYX-ray2.60A/B66-362[»]
3NUNX-ray2.20A67-358[»]
3NUSX-ray2.75A73-358[»]
3NUUX-ray1.98A73-358[»]
3NUYX-ray2.10A73-358[»]
3ORXX-ray2.20A/B/C/D/E/F/G/H51-359[»]
3ORZX-ray2.00A/B/C/D51-359[»]
3OTUX-ray2.10A51-359[»]
3PWYX-ray3.50A51-359[»]
3QC4X-ray1.80A/B51-359[»]
3QCQX-ray2.50A48-359[»]
3QCSX-ray2.49A48-359[»]
3QCXX-ray2.30A48-359[»]
3QCYX-ray2.20A48-359[»]
3QD0X-ray1.99A48-359[»]
3QD3X-ray2.00A48-359[»]
3QD4X-ray2.30A48-359[»]
3RCJX-ray1.70A50-359[»]
3RWPX-ray1.92A51-359[»]
3RWQX-ray2.55A51-359[»]
3SC1X-ray2.70A50-359[»]
4A06X-ray2.00A50-359[»]
4A07X-ray1.85A50-359[»]
4AW0X-ray1.43A51-359[»]
4AW1X-ray1.68A51-359[»]
4CT1X-ray1.85A50-359[»]
4CT2X-ray1.25A50-359[»]
4RQKX-ray1.55A50-359[»]
4RQVX-ray1.50A50-359[»]
4RRVX-ray1.41A50-359[»]
ProteinModelPortaliO15530.
SMRiO15530. Positions 71-556.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO15530.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini82 – 342261Protein kinasePROSITE-ProRule annotationAdd
BLAST
Domaini459 – 55092PHAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni113 – 15745PIF-pocket1 PublicationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi389 – 39810Poly-Ser

Domaini

The PH domain plays a pivotal role in the localization and nuclear import of PDPK1 and is also essential for its homodimerization.
The PIF-pocket is a small lobe in the catalytic domain required by the enzyme for the binding to the hydrophobic motif of its substrates. It is an allosteric regulatory site that can accommodate small compounds acting as allosteric inhibitors.1 Publication

Sequence similaritiesi

Contains 1 PH domain.Curated
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00550000074819.
HOGENOMiHOG000233026.
HOVERGENiHBG098357.
InParanoidiO15530.
KOiK06276.
OMAiEIPWSLE.
OrthoDBiEOG7R56S4.
PhylomeDBiO15530.
TreeFamiTF105423.

Family and domain databases

Gene3Di2.30.29.30. 2 hits.
InterProiIPR011009. Kinase-like_dom.
IPR011993. PH_like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O15530-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MARTTSQLYD AVPIQSSVVL CSCPSPSMVR TQTESSTPPG IPGGSRQGPA
60 70 80 90 100
MDGTAAEPRP GAGSLQHAQP PPQPRKKRPE DFKFGKILGE GSFSTVVLAR
110 120 130 140 150
ELATSREYAI KILEKRHIIK ENKVPYVTRE RDVMSRLDHP FFVKLYFTFQ
160 170 180 190 200
DDEKLYFGLS YAKNGELLKY IRKIGSFDET CTRFYTAEIV SALEYLHGKG
210 220 230 240 250
IIHRDLKPEN ILLNEDMHIQ ITDFGTAKVL SPESKQARAN SFVGTAQYVS
260 270 280 290 300
PELLTEKSAC KSSDLWALGC IIYQLVAGLP PFRAGNEYLI FQKIIKLEYD
310 320 330 340 350
FPEKFFPKAR DLVEKLLVLD ATKRLGCEEM EGYGPLKAHP FFESVTWENL
360 370 380 390 400
HQQTPPKLTA YLPAMSEDDE DCYGNYDNLL SQFGCMQVSS SSSSHSLSAS
410 420 430 440 450
DTGLPQRSGS NIEQYIHDLD SNSFELDLQF SEDEKRLLLE KQAGGNPWHQ
460 470 480 490 500
FVENNLILKM GPVDKRKGLF ARRRQLLLTE GPHLYYVDPV NKVLKGEIPW
510 520 530 540 550
SQELRPEAKN FKTFFVHTPN RTYYLMDPSG NAHKWCRKIQ EVWRQRYQSH

PDAAVQ
Length:556
Mass (Da):63,152
Last modified:January 1, 1998 - v1
Checksum:iED8C0306DC4D0653
GO
Isoform 2 (identifier: O15530-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-50: Missing.

Show »
Length:506
Mass (Da):58,035
Checksum:i22D376B8A13FD3F3
GO
Isoform 3 (identifier: O15530-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     238-263: Missing.

Show »
Length:530
Mass (Da):60,396
Checksum:iCEAF882CBD3EB1F2
GO
Isoform 4 (identifier: O15530-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     110-237: IKILEKRHII...KVLSPESKQA → T

Show »
Length:429
Mass (Da):48,201
Checksum:i860C8A8C06161CE1
GO
Isoform 5 (identifier: O15530-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     448-556: WHQFVENNLI...YQSHPDAAVQ → CLTGRII

Note: No experimental confirmation available.
Show »
Length:454
Mass (Da):50,838
Checksum:i8D812DCC8CED2998
GO

Sequence cautioni

The sequence BAD93072.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 5050Missing in isoform 2. CuratedVSP_004894Add
BLAST
Alternative sequencei110 – 237128IKILE…ESKQA → T in isoform 4. 1 PublicationVSP_041902Add
BLAST
Alternative sequencei238 – 26326Missing in isoform 3. 1 PublicationVSP_004895Add
BLAST
Alternative sequencei448 – 556109WHQFV…DAAVQ → CLTGRII in isoform 5. 1 PublicationVSP_044796Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF017995 mRNA. Translation: AAC51825.1.
Y15056 mRNA. Translation: CAA75341.1.
CR536517 mRNA. Translation: CAG38755.1.
AB209835 mRNA. Translation: BAD93072.1. Different initiation.
AC093525 Genomic DNA. No translation available.
AC141586 Genomic DNA. No translation available.
BC006339 mRNA. Translation: AAH06339.2.
BC012103 mRNA. Translation: AAH12103.1.
BC033494 mRNA. Translation: AAH33494.1.
CCDSiCCDS10472.1. [O15530-1]
CCDS10473.1. [O15530-4]
CCDS58411.1. [O15530-5]
RefSeqiNP_001248745.1. NM_001261816.1. [O15530-5]
NP_002604.1. NM_002613.4. [O15530-1]
NP_112558.2. NM_031268.5. [O15530-4]
UniGeneiHs.459691.

Genome annotation databases

EnsembliENST00000268673; ENSP00000268673; ENSG00000140992. [O15530-4]
ENST00000342085; ENSP00000344220; ENSG00000140992. [O15530-1]
ENST00000441549; ENSP00000395357; ENSG00000140992. [O15530-5]
GeneIDi5170.
KEGGihsa:5170.
UCSCiuc002cqs.4. human. [O15530-1]
uc002cqt.4. human. [O15530-4]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF017995 mRNA. Translation: AAC51825.1.
Y15056 mRNA. Translation: CAA75341.1.
CR536517 mRNA. Translation: CAG38755.1.
AB209835 mRNA. Translation: BAD93072.1. Different initiation.
AC093525 Genomic DNA. No translation available.
AC141586 Genomic DNA. No translation available.
BC006339 mRNA. Translation: AAH06339.2.
BC012103 mRNA. Translation: AAH12103.1.
BC033494 mRNA. Translation: AAH33494.1.
CCDSiCCDS10472.1. [O15530-1]
CCDS10473.1. [O15530-4]
CCDS58411.1. [O15530-5]
RefSeqiNP_001248745.1. NM_001261816.1. [O15530-5]
NP_002604.1. NM_002613.4. [O15530-1]
NP_112558.2. NM_031268.5. [O15530-4]
UniGeneiHs.459691.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1H1WX-ray2.00A71-359[»]
1OKYX-ray2.30A51-360[»]
1OKZX-ray2.51A51-360[»]
1UU3X-ray1.70A51-360[»]
1UU7X-ray1.90A51-360[»]
1UU8X-ray2.50A51-360[»]
1UU9X-ray1.95A72-357[»]
1UVRX-ray2.81A71-359[»]
1W1DX-ray1.50A409-556[»]
1W1GX-ray1.45A409-556[»]
1W1HX-ray1.45A/B/C/D409-556[»]
1Z5MX-ray2.17A74-359[»]
2BIYX-ray1.95A51-360[»]
2PE0X-ray2.35A74-359[»]
2PE1X-ray2.14A74-359[»]
2PE2X-ray2.13A74-359[»]
2R7BX-ray2.70A48-359[»]
2VKIX-ray1.80A409-556[»]
2XCHX-ray2.00A51-359[»]
2XCKX-ray2.30A51-359[»]
3H9OX-ray2.30A51-359[»]
3HRCX-ray1.91A50-359[»]
3HRFX-ray1.90A50-359[»]
3IONX-ray2.40A48-359[»]
3IOPX-ray2.20A48-359[»]
3NAXX-ray1.75A66-362[»]
3NAYX-ray2.60A/B66-362[»]
3NUNX-ray2.20A67-358[»]
3NUSX-ray2.75A73-358[»]
3NUUX-ray1.98A73-358[»]
3NUYX-ray2.10A73-358[»]
3ORXX-ray2.20A/B/C/D/E/F/G/H51-359[»]
3ORZX-ray2.00A/B/C/D51-359[»]
3OTUX-ray2.10A51-359[»]
3PWYX-ray3.50A51-359[»]
3QC4X-ray1.80A/B51-359[»]
3QCQX-ray2.50A48-359[»]
3QCSX-ray2.49A48-359[»]
3QCXX-ray2.30A48-359[»]
3QCYX-ray2.20A48-359[»]
3QD0X-ray1.99A48-359[»]
3QD3X-ray2.00A48-359[»]
3QD4X-ray2.30A48-359[»]
3RCJX-ray1.70A50-359[»]
3RWPX-ray1.92A51-359[»]
3RWQX-ray2.55A51-359[»]
3SC1X-ray2.70A50-359[»]
4A06X-ray2.00A50-359[»]
4A07X-ray1.85A50-359[»]
4AW0X-ray1.43A51-359[»]
4AW1X-ray1.68A51-359[»]
4CT1X-ray1.85A50-359[»]
4CT2X-ray1.25A50-359[»]
4RQKX-ray1.55A50-359[»]
4RQVX-ray1.50A50-359[»]
4RRVX-ray1.41A50-359[»]
ProteinModelPortaliO15530.
SMRiO15530. Positions 71-556.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111196. 52 interactions.
DIPiDIP-38372N.
IntActiO15530. 49 interactions.
MINTiMINT-1371493.
STRINGi9606.ENSP00000344220.

Chemistry

BindingDBiO15530.
ChEMBLiCHEMBL2534.
DrugBankiDB00482. Celecoxib.
GuidetoPHARMACOLOGYi1519.

PTM databases

PhosphoSiteiO15530.

Polymorphism and mutation databases

BioMutaiPDPK1.

Proteomic databases

MaxQBiO15530.
PaxDbiO15530.
PRIDEiO15530.

Protocols and materials databases

DNASUi5170.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000268673; ENSP00000268673; ENSG00000140992. [O15530-4]
ENST00000342085; ENSP00000344220; ENSG00000140992. [O15530-1]
ENST00000441549; ENSP00000395357; ENSG00000140992. [O15530-5]
GeneIDi5170.
KEGGihsa:5170.
UCSCiuc002cqs.4. human. [O15530-1]
uc002cqt.4. human. [O15530-4]

Organism-specific databases

CTDi5170.
GeneCardsiGC16P002587.
H-InvDBHIX0038570.
HIX0038793.
HGNCiHGNC:8816. PDPK1.
HPAiCAB004272.
HPA035199.
MIMi605213. gene.
neXtProtiNX_O15530.
PharmGKBiPA33160.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00550000074819.
HOGENOMiHOG000233026.
HOVERGENiHBG098357.
InParanoidiO15530.
KOiK06276.
OMAiEIPWSLE.
OrthoDBiEOG7R56S4.
PhylomeDBiO15530.
TreeFamiTF105423.

Enzyme and pathway databases

BRENDAi2.7.11.1. 2681.
ReactomeiREACT_12555. Downstream TCR signaling.
REACT_15523. Integrin alphaIIb beta3 signaling.
REACT_163769. Role of LAT2/NTAL/LAB on calcium mobilization.
REACT_163994. FCERI mediated NF-kB activation.
REACT_1695. GPVI-mediated activation cascade.
REACT_188323. CLEC7A (Dectin-1) signaling.
REACT_19290. G beta:gamma signalling through PI3Kgamma.
REACT_19358. CD28 dependent PI3K/Akt signaling.
REACT_19405. CTLA4 inhibitory signaling.
REACT_20510. RSK activation.
REACT_263991. VEGFR2 mediated vascular permeability.
REACT_264273. VEGFR2 mediated cell proliferation.
REACT_355468. Constitutive Signaling by AKT1 E17K in Cancer.
REACT_355542. RHO GTPases activate PKNs.
REACT_75829. PIP3 activates AKT signaling.
REACT_790. Activation of PKB.
SignaLinkiO15530.

Miscellaneous databases

ChiTaRSiPDPK1. human.
EvolutionaryTraceiO15530.
GeneWikiiPhosphoinositide-dependent_kinase-1.
GenomeRNAii5170.
NextBioi20004.
PROiO15530.
SOURCEiSearch...

Gene expression databases

BgeeiO15530.
CleanExiHS_PDK1.
HS_PDPK1.
ExpressionAtlasiO15530. baseline and differential.
GenevisibleiO15530. HS.

Family and domain databases

Gene3Di2.30.29.30. 2 hits.
InterProiIPR011009. Kinase-like_dom.
IPR011993. PH_like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase B alpha."
    Alessi D.R., James S.R., Downes C.P., Holmes A.B., Gaffney P.R.J., Reese C.B., Cohen P.
    Curr. Biol. 7:261-269(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION IN PHOSPHORYLATION OF PKB/AKT1.
  2. "3-phosphoinositide-dependent protein kinase-1 (PDK1): structural and functional homology with the Drosophila DSTPK61 kinase."
    Alessi D.R., Deak M., Casamayor A., Caudwell F.B., Morrice N.A., Norman D.G., Gaffney P.R.J., Reese C.B., MacDougall C.N., Harbison D., Ashworth A., Bownes M.
    Curr. Biol. 7:776-789(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  3. "Protein kinase B kinases that mediate phosphatidylinositol 3,4,5-trisphosphate-dependent activation of protein kinase B."
    Stephens L.R., Anderson K.E., Stokoe D., Erdjument-Bromage H., Painter G.F., Holmes A.B., Gaffney P.R.J., Reese C.B., McCormick F., Tempst P., Coadwell W.J., Hawkins P.T.
    Science 279:710-714(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3).
    Tissue: Myeloid.
  4. "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
    Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
    Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
  5. "Homo sapiens protein coding cDNA."
    Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F.
    Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
    Tissue: Brain.
  6. "The sequence and analysis of duplication-rich human chromosome 16."
    Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.
    , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A.
    Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  7. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 4).
    Tissue: Brain, Kidney and Uterus.
  8. Bienvenut W.V., Waridel P., Quadroni M.
    Submitted (MAR-2009) to UniProtKB
    Cited for: PROTEIN SEQUENCE OF 60-75; 87-100; 184-199; 239-257 AND 284-293, PHOSPHORYLATION AT SER-241, IDENTIFICATION BY MASS SPECTROMETRY.
    Tissue: Embryonic kidney.
  9. "Translocation of PDK-1 to the plasma membrane is important in allowing PDK-1 to activate protein kinase B."
    Anderson K.E., Coadwell W.J., Stephens L.R., Hawkins P.T.
    Curr. Biol. 8:684-691(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF ARG-474, ALTERNATIVE SPLICING.
  10. Cited for: FUNCTION IN PHOSPHORYLATION OF PRKCZ.
  11. "Phosphorylation and activation of cAMP-dependent protein kinase by phosphoinositide-dependent protein kinase."
    Cheng X., Ma Y., Moore M., Hemmings B.A., Taylor S.S.
    Proc. Natl. Acad. Sci. U.S.A. 95:9849-9854(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF PRKACA.
  12. Cited for: FUNCTION IN PHOSPHORYLATION OF RPS6KB1.
  13. "Phosphorylation of Ser-241 is essential for the activity of 3-phosphoinositide-dependent protein kinase-1: identification of five sites of phosphorylation in vivo."
    Casamayor A., Morrice N.A., Alessi D.R.
    Biochem. J. 342:287-292(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-25; SER-241; SER-393; SER-396 AND SER-410, MUTAGENESIS OF SER-25; SER-241; SER-393; SER-396 AND SER-410.
  14. "A PDK1 homolog is necessary and sufficient to transduce AGE-1 PI3 kinase signals that regulate diapause in Caenorhabditis elegans."
    Paradis S., Ailion M., Toker A., Thomas J.H., Ruvkun G.
    Genes Dev. 13:1438-1452(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF ALA-277.
  15. "90-kDa ribosomal S6 kinase is phosphorylated and activated by 3-phosphoinositide-dependent protein kinase-1."
    Jensen C.J., Buch M.-B., Krag T.O., Hemmings B.A., Gammeltoft S., Froedin M.
    J. Biol. Chem. 274:27168-27176(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF RPS6KA3.
  16. "p21-activated kinase (PAK1) is phosphorylated and activated by 3-phosphoinositide-dependent kinase-1 (PDK1)."
    King C.C., Gardiner E.M., Zenke F.T., Bohl B.P., Newton A.C., Hemmings B.A., Bokoch G.M.
    J. Biol. Chem. 275:41201-41209(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF PAK1, INTERACTION WITH PAK1.
  17. "Identification of tyrosine phosphorylation sites on 3-phosphoinositide-dependent protein kinase-1 (PDK1) and their role in regulating kinase activity."
    Park J., Hill M.M., Hess D., Brazil D.P., Hofsteenge J., Hemmings B.A.
    J. Biol. Chem. 276:37459-37471(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT TYR-9; SER-241; TYR-373 AND TYR-376, MUTAGENESIS OF TYR-9; TYR-373 AND TYR-376.
  18. "Regulation of kinase activity of 3-phosphoinositide-dependent protein kinase-1 by binding to 14-3-3."
    Sato S., Fujita N., Tsuruo T.
    J. Biol. Chem. 277:39360-39367(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: ENZYME REGULATION, INTERACTION WITH YWHAH AND YWHAQ.
  19. "Multiple phosphoinositide 3-kinase-dependent steps in activation of protein kinase B."
    Scheid M.P., Marignani P.A., Woodgett J.R.
    Mol. Cell. Biol. 22:6247-6260(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF PKB/AKT1.
  20. "Pyk2- and Src-dependent tyrosine phosphorylation of PDK1 regulates focal adhesions."
    Taniyama Y., Weber D.S., Rocic P., Hilenski L., Akers M.L., Park J., Hemmings B.A., Alexander R.W., Griendling K.K.
    Mol. Cell. Biol. 23:8019-8029(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, PHOSPHORYLATION AT TYR-9; TYR-373 AND TYR-376 BY SRC, INTERACTION WITH PTK2B, SUBCELLULAR LOCATION.
  21. "Peroxisomal targeting as a tool for assaying protein-protein interactions in the living cell: cytokine-independent survival kinase (CISK) binds PDK-1 in vivo in a phosphorylation-dependent manner."
    Nilsen T., Slagsvold T., Skjerpen C.S., Brech A., Stenmark H., Olsnes S.
    J. Biol. Chem. 279:4794-4801(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF SGK3, INTERACTION WITH SGK3.
  22. "The adaptor protein Grb14 regulates the localization of 3-phosphoinositide-dependent kinase-1."
    King C.C., Newton A.C.
    J. Biol. Chem. 279:37518-37527(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, INTERACTION WITH GRB14.
  23. "PDK1 acquires PDK2 activity in the presence of a synthetic peptide derived from the carboxyl terminus of PRK2."
    Balendran A., Casamayor A., Deak M., Paterson A., Gaffney P., Currie R., Downes C.P., Alessi D.R.
    Curr. Biol. 9:393-404(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF AKT1, INTERACTION WITH PKN2.
  24. "PDK1, the master regulator of AGC kinase signal transduction."
    Mora A., Komander D., van Aalten D.M., Alessi D.R.
    Semin. Cell Dev. Biol. 15:161-170(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON FUNCTION.
  25. "3-Phosphoinositide-dependent protein kinase-1-mediated IkappaB kinase beta (IkkB) phosphorylation activates NF-kappaB signaling."
    Tanaka H., Fujita N., Tsuruo T.
    J. Biol. Chem. 280:40965-40973(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF IKKB, INTERACTION WITH IKKB.
  26. "Regulation of transforming growth factor-beta signaling and PDK1 kinase activity by physical interaction between PDK1 and serine-threonine kinase receptor-associated protein."
    Seong H.A., Jung H., Choi H.S., Kim K.T., Ha H.
    J. Biol. Chem. 280:42897-42908(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, ENZYME REGULATION, INTERACTION WITH STRAP.
  27. "Phosphoinositide-dependent phosphorylation of PDK1 regulates nuclear translocation."
    Scheid M.P., Parsons M., Woodgett J.R.
    Mol. Cell. Biol. 25:2347-2363(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-396, SUBCELLULAR LOCATION.
  28. "Tyrosine phosphorylation of phosphoinositide-dependent kinase 1 by the insulin receptor is necessary for insulin metabolic signaling."
    Fiory F., Alberobello A.T., Miele C., Oriente F., Esposito I., Corbo V., Ruvo M., Tizzano B., Rasmussen T.E., Gammeltoft S., Formisano P., Beguinot F.
    Mol. Cell. Biol. 25:10803-10814(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT TYR-9; TYR-373 AND TYR-376 BY INSR, INTERACTION WITH INSR.
  29. "Role of the PH domain in regulating in vitro autophosphorylation events required for reconstitution of PDK1 catalytic activity."
    Gao X., Harris T.K.
    Bioorg. Chem. 34:200-223(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-241 AND THR-513.
  30. "3-Phosphoinositide-dependent PDK1 negatively regulates transforming growth factor-beta-induced signaling in a kinase-dependent manner through physical interaction with Smad proteins."
    Seong H.A., Jung H., Kim K.T., Ha H.
    J. Biol. Chem. 282:12272-12289(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH SMAD2; SMAD3; SMAD4 AND SMAD7.
  31. "Essential role of PDK1 in regulating endothelial cell migration."
    Primo L., di Blasio L., Roca C., Droetto S., Piva R., Schaffhausen B., Bussolino F.
    J. Cell Biol. 176:1035-1047(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.
  32. "The C-terminus of PRK2/PKNgamma is required for optimal activation by RhoA in a GTP-dependent manner."
    Lim W.G., Chen X., Liu J.P., Tan B.J., Zhou S., Smith A., Lees N., Hou L., Gu F., Yu X.Y., Du Y., Smith D., Verma C., Liu K., Duan W.
    Arch. Biochem. Biophys. 479:170-178(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF PKN2.
  33. "TUSC4/NPRL2, a novel PDK1-interacting protein, inhibits PDK1 tyrosine phosphorylation and its downstream signaling."
    Kurata A., Katayama R., Watanabe T., Tsuruo T., Fujita N.
    Cancer Sci. 99:1827-1834(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH NPRL2, ENZYME REGULATION.
  34. "Dissecting the role of the 3-phosphoinositide-dependent protein kinase-1 (PDK1) signalling pathways."
    Bayascas J.R.
    Cell Cycle 7:2978-2982(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON FUNCTION.
  35. "Regulation of 3-phosphoinositide-dependent protein kinase-1 (PDK1) by Src involves tyrosine phosphorylation of PDK1 and Src homology 2 domain binding."
    Yang K.J., Shin S., Piao L., Shin E., Li Y., Park K.A., Byun H.S., Won M., Hong J., Kweon G.R., Hur G.M., Seok J.H., Chun T., Brazil D.P., Hemmings B.A., Park J.
    J. Biol. Chem. 283:1480-1491(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SRC; RASA1 AND CRK, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  36. "The nuclear localization of 3'-phosphoinositide-dependent kinase-1 is dependent on its association with the protein tyrosine phosphatase SHP-1."
    Sephton C.F., Zhang D., Lehmann T.M., Pennington P.R., Scheid M.P., Mousseau D.D.
    Cell. Signal. 21:1634-1644(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, INTERACTION WITH PTPN6.
  37. "IGF-I regulated phosphorylation and translocation of PDK-1 in neurons."
    Alajajian B.B., Fletcher L., Isgor E., Jimenez D.F., Digicaylioglu M.
    NeuroReport 20:579-583(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  38. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
    Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
    Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Leukemic T-cell.
  39. "PDK1 phosphorylation at Thr354 by murine protein serine/threonine kinase 38 contributes to the negative regulation of PDK1 activity."
    Seong H.A., Jung H., Manoharan R., Ha H.
    J. Biol. Chem. 287:20811-20822(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT THR-354 BY MELK, PHOSPHORYLATION AT SER-394 AND SER-398 BY MAP3K5, MUTAGENESIS OF THR-354; SER-394 AND SER-398.
  40. "Ubiquitin-specific protease 4 inhibits mono-ubiquitination of the master growth factor signaling kinase PDK1."
    Uras I.Z., List T., Nijman S.M.
    PLoS ONE 7:E31003-E31003(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: UBIQUITINATION, DEUBIQUITINATION BY USP4.
  41. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  42. "High resolution crystal structure of the human PDK1 catalytic domain defines the regulatory phosphopeptide docking site."
    Biondi R.M., Komander D., Thomas C.C., Lizcano J.M., Deak M., Alessi D.R., van Aalten D.M.
    EMBO J. 21:4219-4228(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 71-359 IN COMPLEX WITH ATP.
  43. "Role of T-loop phosphorylation in PDK1 activation, stability, and substrate binding."
    Komander D., Kular G., Deak M., Alessi D.R., van Aalten D.M.
    J. Biol. Chem. 280:18797-18802(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 51-360 IN COMPLEX WITH ATP.
  44. Cited for: X-RAY CRYSTALLOGRAPHY (2.17 ANGSTROMS) OF 74-359, PHOSPHORYLATION AT SER-241.
  45. "Regulation of 3-phosphoinositide-dependent protein kinase 1 activity by homodimerization in live cells."
    Masters T.A., Calleja V., Armoogum D.A., Marsh R.J., Applebee C.J., Laguerre M., Bain A.J., Larijani B.
    Sci. Signal. 3:RA78-RA78(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 409-556, SUBUNIT, ENZYME REGULATION, MUTAGENESIS OF THR-513.
  46. "Substrate-selective inhibition of protein kinase PDK1 by small compounds that bind to the PIF-pocket allosteric docking site."
    Busschots K., Lopez-Garcia L.A., Lammi C., Stroba A., Zeuzem S., Piiper A., Alzari P.M., Neimanis S., Arencibia J.M., Engel M., Schulze J.O., Biondi R.M.
    Chem. Biol. 19:1152-1163(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.43 ANGSTROMS) OF 51-359 IN COMPLEX WITH ATP, DOMAIN.

Entry informationi

Entry nameiPDPK1_HUMAN
AccessioniPrimary (citable) accession number: O15530
Secondary accession number(s): H0Y4Z0
, Q59EH6, Q6FI20, Q8IV52, Q9BRD5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 18, 2001
Last sequence update: January 1, 1998
Last modified: June 24, 2015
This is version 176 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.