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O15530 (PDPK1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 166. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
3-phosphoinositide-dependent protein kinase 1

Short name=hPDK1
EC=2.7.11.1
Gene names
Name:PDPK1
Synonyms:PDK1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length556 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1 Ref.10 Ref.11 Ref.12 Ref.15 Ref.16 Ref.19 Ref.20 Ref.21 Ref.23 Ref.25 Ref.26 Ref.30 Ref.31 Ref.32

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulation

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. Ref.18 Ref.26 Ref.33 Ref.41

Subunit structure

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. Ref.16 Ref.18 Ref.20 Ref.21 Ref.22 Ref.23 Ref.25 Ref.26 Ref.28 Ref.30 Ref.33 Ref.35 Ref.36 Ref.41

Subcellular location

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. Ref.20 Ref.22 Ref.27 Ref.31 Ref.35 Ref.36 Ref.37

Tissue specificity

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. Ref.35

Induction

Stimulated by insulin, and the oxidants hydrogen peroxide and peroxovanadate. Ref.18 Ref.26 Ref.33 Ref.41

Domain

The PH domain plays a pivotal role in the localization and nuclear import of PDPK1 and is also essential for its homodimerization.

Post-translational modification

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. Ref.8 Ref.13 Ref.17 Ref.20 Ref.27 Ref.28 Ref.29 Ref.39

Autophosphorylated; autophosphorylation is inhibited by the apoptotic C-terminus cleavage product of PKN2 By similarity. Ref.8 Ref.13 Ref.17 Ref.20 Ref.27 Ref.28 Ref.29 Ref.39

Monoubiquitinated in the kinase domain, deubiquitinated by USP4.

Sequence similarities

Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PDPK1 subfamily.

Contains 1 PH domain.

Contains 1 protein kinase domain.

Sequence caution

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

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCell junction
Cell membrane
Cytoplasm
Membrane
Nucleus
   Coding sequence diversityAlternative splicing
   LigandATP-binding
Nucleotide-binding
   Molecular functionActivator
Kinase
Serine/threonine-protein kinase
Transferase
   PTMAcetylation
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processFc-epsilon receptor signaling pathway

Traceable author statement. Source: Reactome

T cell costimulation

Traceable author statement. Source: Reactome

T cell receptor signaling pathway

Traceable author statement. Source: Reactome

actin cytoskeleton organization

Traceable author statement PubMed 10792047. Source: ProtInc

activation of protein kinase B activity

Inferred from direct assay Ref.2. Source: BHF-UCL

blood coagulation

Traceable author statement. Source: Reactome

cell migration

Inferred from mutant phenotype PubMed 22454520. Source: BHF-UCL

cellular response to epidermal growth factor stimulus

Inferred from mutant phenotype PubMed 22454520. Source: BHF-UCL

cellular response to insulin stimulus

Inferred from mutant phenotype PubMed 10567711. Source: BHF-UCL

epidermal growth factor receptor signaling pathway

Inferred from mutant phenotype PubMed 22454520. Source: BHF-UCL

extrinsic apoptotic signaling pathway

Inferred from mutant phenotype Ref.25. Source: UniProtKB

fibroblast growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

focal adhesion assembly

Inferred from electronic annotation. Source: Ensembl

hyperosmotic response

Inferred from electronic annotation. Source: Ensembl

innate immune response

Traceable author statement. Source: Reactome

insulin receptor signaling pathway

Traceable author statement. Source: Reactome

intracellular signal transduction

Inferred from direct assay PubMed 14749367. Source: MGI

negative regulation of cardiac muscle cell apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of protein kinase activity

Inferred from direct assay PubMed 9373175. Source: BHF-UCL

negative regulation of toll-like receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

negative regulation of transforming growth factor beta receptor signaling pathway

Inferred from direct assay Ref.30. Source: UniProtKB

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

peptidyl-threonine phosphorylation

Inferred from direct assay Ref.2. Source: BHF-UCL

phosphatidylinositol-mediated signaling

Traceable author statement. Source: Reactome

platelet activation

Traceable author statement. Source: Reactome

positive regulation of establishment of protein localization to plasma membrane

Inferred from mutant phenotype PubMed 10567711. Source: BHF-UCL

positive regulation of phospholipase activity

Inferred from mutant phenotype PubMed 22454520. Source: BHF-UCL

positive regulation of release of sequestered calcium ion into cytosol

Inferred from direct assay PubMed 22454520. Source: BHF-UCL

protein autophosphorylation

Traceable author statement Ref.24. Source: UniProtKB

protein phosphorylation

Inferred from direct assay Ref.20. Source: UniProtKB

regulation of I-kappaB kinase/NF-kappaB signaling

Inferred from mutant phenotype Ref.25. Source: UniProtKB

regulation of endothelial cell migration

Inferred from electronic annotation. Source: Ensembl

regulation of mast cell degranulation

Inferred from electronic annotation. Source: Ensembl

regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

synaptic transmission

Traceable author statement. Source: Reactome

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

type B pancreatic cell development

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcell projection

Inferred from direct assay PubMed 22454520. Source: BHF-UCL

cytoplasm

Inferred from direct assay Ref.9. Source: UniProtKB

cytoplasmic membrane-bounded vesicle

Inferred from electronic annotation. Source: Ensembl

cytosol

Traceable author statement. Source: Reactome

focal adhesion

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleoplasm

Traceable author statement. Source: Reactome

plasma membrane

Inferred from direct assay Ref.9. Source: UniProtKB

   Molecular_function3-phosphoinositide-dependent protein kinase activity

Inferred from direct assay Ref.2. Source: BHF-UCL

ATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

kinase activity

Inferred from experiment. Source: Reactome

phospholipase activator activity

Inferred from mutant phenotype PubMed 22454520. Source: BHF-UCL

phospholipase binding

Inferred from physical interaction PubMed 22454520. Source: BHF-UCL

protein binding

Inferred from physical interaction PubMed 24705354. Source: IntAct

protein serine/threonine kinase activity

Inferred from direct assay Ref.2. Source: BHF-UCL

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O15530-1)

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.
Isoform 2 (identifier: O15530-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-50: Missing.
Isoform 3 (identifier: O15530-3)

The sequence of this isoform differs from the canonical sequence as follows:
     238-263: Missing.
Isoform 4 (identifier: O15530-4)

The sequence of this isoform differs from the canonical sequence as follows:
     110-237: IKILEKRHII...KVLSPESKQA → T
Isoform 5 (identifier: O15530-5)

The sequence of this isoform differs from the canonical sequence as follows:
     448-556: WHQFVENNLI...YQSHPDAAVQ → CLTGRII
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 5565563-phosphoinositide-dependent protein kinase 1
PRO_0000086500

Regions

Domain82 – 342261Protein kinase
Domain459 – 55092PH
Nucleotide binding88 – 969ATP By similarity
Compositional bias389 – 39810Poly-Ser

Sites

Active site2051Proton acceptor By similarity
Binding site1111ATP By similarity

Amino acid modifications

Modified residue91Phosphotyrosine; by SRC and INSR Ref.17 Ref.20 Ref.28
Modified residue251Phosphoserine Ref.13
Modified residue2411Phosphoserine; by autocatalysis Ref.8 Ref.13 Ref.17 Ref.29
Modified residue3041N6-acetyllysine By similarity
Modified residue3541Phosphothreonine; by MELK Ref.39
Modified residue3731Phosphotyrosine; by SRC and INSR Ref.17 Ref.20 Ref.28
Modified residue3761Phosphotyrosine; by SRC and INSR Ref.17 Ref.20 Ref.28
Modified residue3931Phosphoserine Ref.13
Modified residue3941Phosphoserine; by MAP3K5 Ref.39
Modified residue3961Phosphoserine Ref.13 Ref.27
Modified residue3981Phosphoserine; by MAP3K5 Ref.39
Modified residue4101Phosphoserine Ref.13
Modified residue5011Phosphoserine; by PKC/PRKCQ By similarity
Modified residue5131Phosphothreonine; by autocatalysis Ref.29
Modified residue5291Phosphoserine; by PKC/PRKCQ By similarity

Natural variations

Alternative sequence1 – 5050Missing in isoform 2.
VSP_004894
Alternative sequence110 – 237128IKILE…ESKQA → T in isoform 4.
VSP_041902
Alternative sequence238 – 26326Missing in isoform 3.
VSP_004895
Alternative sequence448 – 556109WHQFV…DAAVQ → CLTGRII in isoform 5.
VSP_044796

Experimental info

Mutagenesis91Y → F: Slight reduction in pervanadate-stimulated tyrosine phosphorylation. Ref.17
Mutagenesis251S → A: No effect. Ref.13
Mutagenesis2411S → A: No activation. Ref.13
Mutagenesis2771A → V: 3-fold increase in kinase activity. Ref.14
Mutagenesis3541T → A: Abolishes phosphorylation by MELK. Ref.39
Mutagenesis3731Y → F: Reduction in basal activity. Ref.17
Mutagenesis3761Y → F: Reduction in basal activity. Ref.17
Mutagenesis3931S → A: No effect. Ref.13
Mutagenesis3941S → A: Abolishes phosphorylation by MAP3K5; when associated with A-398. Ref.39
Mutagenesis3961S → A: No effect. Ref.13
Mutagenesis3981S → A: Abolishes phosphorylation by MAP3K5; when associated with A-394. Ref.39
Mutagenesis4101S → A: No effect. Ref.13
Mutagenesis4741R → A: No PDGF-dependent translocation to the membrane. Ref.9
Mutagenesis5131T → E: Enhanced kinase activity towards PKB. Ref.41

Secondary structure

............................................................................... 556
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 1, 1998. Version 1.
Checksum: ED8C0306DC4D0653

FASTA55663,152
        10         20         30         40         50         60 
MARTTSQLYD AVPIQSSVVL CSCPSPSMVR TQTESSTPPG IPGGSRQGPA MDGTAAEPRP 

        70         80         90        100        110        120 
GAGSLQHAQP PPQPRKKRPE DFKFGKILGE GSFSTVVLAR ELATSREYAI KILEKRHIIK 

       130        140        150        160        170        180 
ENKVPYVTRE RDVMSRLDHP FFVKLYFTFQ DDEKLYFGLS YAKNGELLKY IRKIGSFDET 

       190        200        210        220        230        240 
CTRFYTAEIV SALEYLHGKG IIHRDLKPEN ILLNEDMHIQ ITDFGTAKVL SPESKQARAN 

       250        260        270        280        290        300 
SFVGTAQYVS PELLTEKSAC KSSDLWALGC IIYQLVAGLP PFRAGNEYLI FQKIIKLEYD 

       310        320        330        340        350        360 
FPEKFFPKAR DLVEKLLVLD ATKRLGCEEM EGYGPLKAHP FFESVTWENL HQQTPPKLTA 

       370        380        390        400        410        420 
YLPAMSEDDE DCYGNYDNLL SQFGCMQVSS SSSSHSLSAS DTGLPQRSGS NIEQYIHDLD 

       430        440        450        460        470        480 
SNSFELDLQF SEDEKRLLLE KQAGGNPWHQ FVENNLILKM GPVDKRKGLF ARRRQLLLTE 

       490        500        510        520        530        540 
GPHLYYVDPV NKVLKGEIPW SQELRPEAKN FKTFFVHTPN RTYYLMDPSG NAHKWCRKIQ 

       550 
EVWRQRYQSH PDAAVQ 

« Hide

Isoform 2 [UniParc].

Checksum: 22D376B8A13FD3F3
Show »

FASTA50658,035
Isoform 3 [UniParc].

Checksum: CEAF882CBD3EB1F2
Show »

FASTA53060,396
Isoform 4 [UniParc].

Checksum: 860C8A8C06161CE1
Show »

FASTA42948,201
Isoform 5 [UniParc].

Checksum: 8D812DCC8CED2998
Show »

FASTA45450,838

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"Regulation of protein kinase C zeta by PI 3-kinase and PDK-1."
Chou M.M., Hou W., Johnson J., Graham L.K., Lee M.H., Chen C.S., Newton A.C., Schaffhausen B.S., Toker A.
Curr. Biol. 8:1069-1077(1998) [PubMed] [Europe PMC] [Abstract]
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]"Phosphorylation and activation of p70s6k by PDK1."
Pullen N., Dennis P.B., Andjelkovic M., Dufner A., Kozma S.C., Hemmings B.A., Thomas G.
Science 279:707-710(1998) [PubMed] [Europe PMC] [Abstract]
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]"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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS10472.1. [O15530-1]
CCDS10473.1. [O15530-4]
CCDS58411.1. [O15530-5]
RefSeqNP_001248745.1. NM_001261816.1. [O15530-5]
NP_002604.1. NM_002613.4. [O15530-1]
NP_112558.2. NM_031268.5. [O15530-4]
UniGeneHs.459691.

3D structure databases

PDBe
RCSB-PDB
PDBj
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[»]
ProteinModelPortalO15530.
SMRO15530. Positions 75-556.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111196. 47 interactions.
IntActO15530. 43 interactions.
MINTMINT-1371493.
STRING9606.ENSP00000344220.

Chemistry

BindingDBO15530.
ChEMBLCHEMBL2534.
DrugBankDB00482. Celecoxib.
GuidetoPHARMACOLOGY1519.

PTM databases

PhosphoSiteO15530.

Proteomic databases

MaxQBO15530.
PaxDbO15530.
PRIDEO15530.

Protocols and materials databases

DNASU5170.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000268673; ENSP00000268673; ENSG00000140992. [O15530-4]
ENST00000342085; ENSP00000344220; ENSG00000140992. [O15530-1]
ENST00000441549; ENSP00000395357; ENSG00000140992. [O15530-5]
GeneID5170.
KEGGhsa:5170.
UCSCuc002cqs.4. human. [O15530-1]
uc002cqt.4. human. [O15530-4]

Organism-specific databases

CTD5170.
GeneCardsGC16P002587.
H-InvDBHIX0038570.
HIX0038793.
HGNCHGNC:8816. PDPK1.
HPACAB004272.
HPA035199.
MIM605213. gene.
neXtProtNX_O15530.
PharmGKBPA33160.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233026.
HOVERGENHBG098357.
InParanoidO15530.
KOK06276.
OMASEDMHIQ.
OrthoDBEOG7R56S4.
PhylomeDBO15530.
TreeFamTF105423.

Enzyme and pathway databases

BRENDA2.7.11.1. 2681.
ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_13685. Neuronal System.
REACT_604. Hemostasis.
REACT_6900. Immune System.
SignaLinkO15530.

Gene expression databases

ArrayExpressO15530.
BgeeO15530.
CleanExHS_PDK1.
HS_PDPK1.
GenevestigatorO15530.

Family and domain databases

Gene3D2.30.29.30. 2 hits.
InterProIPR011009. Kinase-like_dom.
IPR011993. PH_like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPDPK1. human.
EvolutionaryTraceO15530.
GeneWikiPhosphoinositide-dependent_kinase-1.
GenomeRNAi5170.
NextBio20004.
PROO15530.
SOURCESearch...

Entry information

Entry namePDPK1_HUMAN
AccessionPrimary (citable) accession number: O15530
Secondary accession number(s): H0Y4Z0 expand/collapse secondary AC list , Q59EH6, Q6FI20, Q8IV52, Q9BRD5
Entry history
Integrated into UniProtKB/Swiss-Prot: October 18, 2001
Last sequence update: January 1, 1998
Last modified: July 9, 2014
This is version 166 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM