Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures
Basic Information
Protein Name :  3-phosphoinositide-dependent protein kinase 1  

UniProtKB / Swiss-Prot ID :  PDPK1_HUMAN

Gene Name (Synonyms) : 
PDPK1, PDK1  

Species :  Homo sapiens (Human). 

Subcellular Localization :  Cytoplasm. Nucleus. Cell membrane; Peripheral membrane protein. Cell junction, focal adhesion. Note=Tyrosine phosphorylation seems to occur only at the cell membrane. Translocates to the cell membrane following insulin stimulation by a mechanism that inv 

Protein 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 Ca(2+) entry and Ca(2+)-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. 

Protein Sequence MARTTSQLYDAVPIQSSVVLCSCPSPSMVRTQTESSTPPGIPGGSRQGPAMDGTAAEPRPGAGSLQHAQP...
Predicted Secondary Structure CCCCCCCHHCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCC...
Protein Variant -
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Overview of Protein Modification Sites with Functional and Structural Information
Accessible Surface Area (ASA)
Pred. Secondary
Real Secondary
Disorder Prediction
Protein Domain
&
Experimental PTM Sites
Predicted PTM Sites
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Experimental Post-Translational Modification Sites Download
Locations
Modification
Substrate Sites
&
Secondary Structure
Accessible Surface Area (%)
Resource
Reference
Structural Characterization
Orthologous
Protein Cluster
9PhosphotyrosineTSQLYDAVP
CCCHHCCCC
8.33Phosphositeplus
Link-
9Phosphotyrosine (RET;SRC)TSQLYDAVP
CCCHHCCCC
8.33PhosphoELM
Link-
9Phosphotyrosine (SRC)TSQLYDAVP
CCCHHCCCC
8.33HPRD
Link-
9Phosphotyrosine; by SRC and INSR.TSQLYDAVP
CCCHHCCCC
8.33UniProtKB
Link-
22PhosphoserineVVLCSCPSP
CCCCCCCCC
25.54Phosphositeplus
Link-
25PhosphoserineCSCPSPSMV
CCCCCCCCC
33.65HPRD
Link-
25PhosphoserineCSCPSPSMV
CCCCCCCCC
33.65Phosphositeplus
Link-
25Phosphoserine (PDK-1)CSCPSPSMV
CCCCCCCCC
33.65PhosphoELM
Link-
25Phosphoserine.CSCPSPSMV
CCCCCCCCC
33.65UniProtKB
Link-
33Phosphothreonine (PDPK1)VRTQTESST
CCCCCCCCC
36.90HPRD
Link-
35Phosphoserine.TQTESSTPP
CCCCCCCCC
42.79UniProtKB
Link-
37PhosphothreonineTESSTPPGI
CCCCCCCCC
42.66HPRD
Link-
37PhosphothreonineTESSTPPGI
CCCCCCCCC
42.66PhosphoELM
Link-
37PhosphothreonineTESSTPPGI
CCCCCCCCC
42.66Phosphositeplus
Link-
37PhosphothreonineTESSTPPGI
CCCCCCCCC
42.66SysPTM
Link-
37Phosphothreonine.TESSTPPGI
CCCCCCCCC
42.66UniProtKB
Link-
126PhosphotyrosineNKVPYVTRE
HHHHHHHHH
19.90Phosphositeplus
Link
148PhosphothreonineKLYFTFQDD
EEEEEEEEC
13.56Phosphositeplus
Link
160PhosphoserineYFGLSYAKN
EEEEEECCC
24.35Phosphositeplus
Link
161PhosphotyrosineFGLSYAKNG
EEEEECCCC
27.00Phosphositeplus
Link
176PhosphoserineRKIGSFDET
HHCCCCCHH
32.76Phosphositeplus
Link
231PhosphoserineAKVLSPESK
EEEECCCCC
29.61Phosphositeplus
Link
241PhosphoserineARANSFVGT
CEEEEECCC
21.96HPRD
Link
241PhosphoserineARANSFVGT
CEEEEECCC
21.96Phosphositeplus
Link
241PhosphoserineARANSFVGT
CEEEEECCC
21.96SysPTM
Link
241Phosphoserine (PDK-1)ARANSFVGT
CEEEEECCC
21.96PhosphoELM
Link
241Phosphoserine (PDPK1)ARANSFVGT
CEEEEECCC
21.96HPRD
Link
241Phosphoserine; by autocatalysis.ARANSFVGT
CEEEEECCC
21.96UniProtKB
Link
245PhosphothreonineSFVGTAQYV
EECCCHHHC
12.80HPRD
Link
245PhosphothreonineSFVGTAQYV
EECCCHHHC
12.80PhosphoELM
Link
245PhosphothreonineSFVGTAQYV
EECCCHHHC
12.80Phosphositeplus
Link
245PhosphothreonineSFVGTAQYV
EECCCHHHC
12.80SysPTM
Link
245Phosphothreonine.SFVGTAQYV
EECCCHHHC
12.80UniProtKB
Link
248PhosphotyrosineGTAQYVSPE
CCHHHCCHH
10.63Phosphositeplus
Link
255PhosphothreoninePELLTEKSA
HHHHCCCCC
54.73Phosphositeplus
Link
304Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)DFPEKFFPK
CCCCCCCHH
53.17Phosphositeplus
Link
304N6-acetyllysineDFPEKFFPK
CCCCCCCHH
53.17HPRD
Link
304N6-acetyllysineDFPEKFFPK
CCCCCCCHH
53.17Phosphositeplus
Link
304N6-acetyllysine.DFPEKFFPK
CCCCCCCHH
53.17UniProtKB
Link
354PhosphothreonineLHQQTPPKL
HHHCCCCCC
34.68Phosphositeplus
Link
354Phosphothreonine; by MELK.LHQQTPPKL
HHHCCCCCC
34.68UniProtKB
Link
366PhosphoserineLPAMSEDDE
CCCCCCCCC
39.72Phosphositeplus
Link-
373PhosphotyrosineDEDCYGNYD
CCCCCCCCC
22.26Phosphositeplus
Link-
373Phosphotyrosine (SRC)DEDCYGNYD
CCCCCCCCC
22.26HPRD
Link-
373Phosphotyrosine (SRC)DEDCYGNYD
CCCCCCCCC
22.26PhosphoELM
Link-
373Phosphotyrosine; by SRC and INSR.DEDCYGNYD
CCCCCCCCC
22.26UniProtKB
Link-
376PhosphotyrosineCYGNYDNLL
CCCCCCCCC
11.22Phosphositeplus
Link-
376Phosphotyrosine (SRC)CYGNYDNLL
CCCCCCCCC
11.22PhosphoELM
Link-
376Phosphotyrosine; by SRC and INSR.CYGNYDNLL
CCCCCCCCC
11.22UniProtKB
Link-
393PhosphoserineSSSSSSHSL
CCCCCHHHH
33.74HPRD
Link-
393PhosphoserineSSSSSSHSL
CCCCCHHHH
33.74Phosphositeplus
Link-
393Phosphoserine (PDK-1)SSSSSSHSL
CCCCCHHHH
33.74PhosphoELM
Link-
393Phosphoserine.SSSSSSHSL
CCCCCHHHH
33.74UniProtKB
Link-
394PhosphoserineSSSSSHSLS
CCCCHHHHH
21.02Phosphositeplus
Link-
394Phosphoserine; by MAP3K5.SSSSSHSLS
CCCCHHHHH
21.02UniProtKB
Link-
396PhosphoserineSSSHSLSAS
CCHHHHHHH
26.43HPRD
Link-
396PhosphoserineSSSHSLSAS
CCHHHHHHH
26.43Phosphositeplus
Link-
396Phosphoserine (PDK-1)SSSHSLSAS
CCHHHHHHH
26.43PhosphoELM
Link-
396Phosphoserine.SSSHSLSAS
CCHHHHHHH
26.43UniProtKB
Link-
398PhosphoserineSHSLSASDT
HHHHHHHHH
28.83Phosphositeplus
Link-
398Phosphoserine; by MAP3K5.SHSLSASDT
HHHHHHHHH
28.83UniProtKB
Link-
410PhosphoserineQRSGSNIEQ
CCCCCCCCC
35.56HPRD
Link-
410PhosphoserineQRSGSNIEQ
CCCCCCCCC
35.56Phosphositeplus
Link-
410Phosphoserine (PDK-1)QRSGSNIEQ
CCCCCCCCC
35.56PhosphoELM
Link-
410Phosphoserine.QRSGSNIEQ
CCCCCCCCC
35.56UniProtKB
Link-
485Phosphotyrosine (SRC)GPHLYYVDP
CCEEEEECC
9.82HPRD
Link-
501PhosphoserineEIPWSQELR
CCCCCHHHH
14.39HPRD
Link-
501PhosphoserineEIPWSQELR
CCCCCHHHH
14.39Phosphositeplus
Link-
513PhosphothreonineKNFKTFFVH
CCCCEEEEE
20.40Phosphositeplus
Link-
513Phosphothreonine (PDK-1)KNFKTFFVH
CCCCEEEEE
20.40PhosphoELM
Link-
513Phosphothreonine (PDPK1)KNFKTFFVH
CCCCEEEEE
20.40HPRD
Link-
513Phosphothreonine; by autocatalysis.KNFKTFFVH
CCCCEEEEE
20.40UniProtKB
Link-
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Protein-Protein Interactions
      Interacting Protein      
Interaction type
Source ID
      Resource      
      Pubmed ID      
Domain-Domain Interactions
KS6B1_HUMANphysical interactionMINT-14377MINT11438723
AKT1_HUMANphysical interactionMINT-13835MINT11438723
FRAP_HUMANphysical interactionMINT-17466MINT11438723
CDAN1_HUMANphysical interactionEBI-737321
intact16169070
1433F_HUMANin vitro
in vivo
HPRD:05556HPRD12177059
HS90A_HUMANin vitro
in vivo
HPRD:05556HPRD11779851
1433T_HUMANin vitro
in vivo
HPRD:05556HPRD12177059
KPCB_HUMANin vivoHPRD:05556HPRD11376011
AKT1_HUMANin vitro
in vivo
HPRD:05556HPRD11825911
11438723
10698680
12149249
11445557
14500673
11278835
9368760
10226025
AKT2_HUMANin vitro
in vivo
HPRD:05556HPRD12048203
9374542
9512493
KPCE_HUMANin vitro
in vivo
HPRD:05556HPRD11062054
12640464
10945988
KPCD_HUMANin vitro
in vivo
yeast 2-hybrid
HPRD:05556HPRD11781095
11381116
9748166
ITB3_HUMANin vitroHPRD:05556HPRD10896934
KS6A3_HUMANin vivoHPRD:05556HPRD10856237
KPCI_HUMANin vivo
yeast 2-hybrid
HPRD:05556HPRD10764742
KPCZ_HUMANin vitro
in vivo
yeast 2-hybrid
HPRD:05556HPRD11781095
9748166
10764742
11222751
14500673
10357815
PKN1_HUMANin vitro
in vivo
yeast 2-hybrid
HPRD:05556HPRD10764742
10792047
10753910
GNDS_HUMANin vitro
in vivo
HPRD:05556HPRD11889038
KAPCA_HUMANin vitro
yeast 2-hybrid
HPRD:05556HPRD10698939
FRAP_HUMANin vitroHPRD:05556HPRD11438723
KS6A1_HUMANin vitro
in vivo
HPRD:05556HPRD10480933
9430688
SGK1_HUMANin vitro
in vivo
HPRD:05556HPRD10357815
10191262
PKN2_HUMANin vitro
in vivo
HPRD:05556HPRD10753910
PAK1_HUMANin vitroHPRD:05556HPRD10995762
ILK_HUMANin vivoHPRD:05556HPRD11313365
PDPK1_HUMANin vitro
in vivo
HPRD:05556HPRD10455013
15144186
11481331
SGK2_HUMANin vitroHPRD:05556HPRD10548550
SGK3_HUMANin vitroHPRD:05556HPRD10548550
AKT3_HUMANin vitro
in vivo
HPRD:05556HPRD12162751
9512493
KS6B1_HUMANin vitro
in vivo
HPRD:05556HPRD11438723
10601311
9271440
9445476
9427642
KS6B2_HUMANin vitroHPRD:05556HPRD11733037
STRAP_HUMANin vivo
yeast 2-hybrid
HPRD:05556HPRD16251192
PRS23_HUMANyeast 2-hybridHPRD:05556HPRD16169070
CDAN1_HUMANyeast 2-hybridHPRD:05556HPRD16169070
PDK2_HUMANENSP00000344220STRING
KS6B1_HUMANENSP00000344220STRING
AKT3_HUMANENSP00000344220STRING
AKT3_HUMANENSP00000344220STRING
AKT1_HUMANENSP00000344220STRING
KPCI_HUMANENSP00000344220STRING
KPCE_HUMANENSP00000344220STRING
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Disease Reference
Kegg disease
There are no disease associations of PTM sites.
Drug Reference
DrugBank
DB00482Celecoxib
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Related Literatures of Post-Translational Modification
Acetylation
ReferencePubMed
"Lysine acetylation targets protein complexes and co-regulates majorcellular functions.";
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.,Olsen J.V., Mann M.;
Science 325:834-840(2009).
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-304, AND MASS SPECTROMETRY.
Phosphorylation
ReferencePubMed
"Phosphorylation of Ser-241 is essential for the activity of 3-phosphoinositide-dependent protein kinase-1: identification of fivesites of phosphorylation in vivo.";
Casamayor A., Morrice N.A., Alessi D.R.;
Biochem. J. 342:287-292(1999).
Cited for: PHOSPHORYLATION AT SER-25; SER-241; SER-393; SER-396 AND SER-410, ANDMUTAGENESIS OF SER-25; SER-241; SER-393; SER-396 AND SER-410.
"Identification of tyrosine phosphorylation sites on 3-phosphoinositide-dependent protein kinase-1 (PDK1) and their role inregulating kinase activity.";
Park J., Hill M.M., Hess D., Brazil D.P., Hofsteenge J.,Hemmings B.A.;
J. Biol. Chem. 276:37459-37471(2001).
Cited for: PHOSPHORYLATION AT TYR-9; SER-241; TYR-373 AND TYR-376, ANDMUTAGENESIS OF TYR-9; TYR-373 AND TYR-376.
"Pyk2- and Src-dependent tyrosine phosphorylation of PDK1 regulatesfocal 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).
Cited for: FUNCTION, PHOSPHORYLATION AT TYR-9; TYR-373 AND TYR-376 BY SRC,INTERACTION WITH PTK2B, AND SUBCELLULAR LOCATION.
"Large-scale characterization of HeLa cell nuclear phosphoproteins.";
Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J.,Li J., Cohn M.A., Cantley L.C., Gygi S.P.;
Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-241, AND MASSSPECTROMETRY.
"Phosphoinositide-dependent phosphorylation of PDK1 regulates nucleartranslocation.";
Scheid M.P., Parsons M., Woodgett J.R.;
Mol. Cell. Biol. 25:2347-2363(2005).
Cited for: PHOSPHORYLATION AT SER-396, AND SUBCELLULAR LOCATION.
"Tyrosine phosphorylation of phosphoinositide-dependent kinase 1 bythe 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).
Cited for: PHOSPHORYLATION AT TYR-9; TYR-373 AND TYR-376 BY INSR, AND INTERACTIONWITH INSR.
"Global, in vivo, and site-specific phosphorylation dynamics insignaling networks.";
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,Mann M.;
Cell 127:635-648(2006).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-245, AND MASSSPECTROMETRY.
"Phosphoproteomic analysis of the human pituitary.";
Beranova-Giorgianni S., Zhao Y., Desiderio D.M., Giorgianni F.;
Pituitary 9:109-120(2006).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-241, AND MASSSPECTROMETRY.
"Kinase-selective enrichment enables quantitative phosphoproteomics ofthe kinome across the cell cycle.";
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,Greff Z., Keri G., Stemmann O., Mann M.;
Mol. Cell 31:438-448(2008).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-37 AND SER-241, AND MASSSPECTROMETRY.
"A quantitative atlas of mitotic phosphorylation.";
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,Elledge S.J., Gygi S.P.;
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-241, AND MASSSPECTROMETRY.
"Lys-N and trypsin cover complementary parts of the phosphoproteome ina refined SCX-based approach.";
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,Mohammed S.;
Anal. Chem. 81:4493-4501(2009).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-37 AND SER-241, AND MASSSPECTROMETRY.
"Large-scale proteomics analysis of the human kinome.";
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,Mann M., Daub H.;
Mol. Cell. Proteomics 8:1751-1764(2009).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-35 AND SER-241, AND MASSSPECTROMETRY.
"Quantitative phosphoproteomic analysis of T cell receptor signalingreveals 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).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-241, AND MASSSPECTROMETRY.
"PDK1 phosphorylation at Thr354 by murine protein serine/threoninekinase 38 contributes to the negative regulation of PDK1 activity.";
Seong H.A., Jung H., Manoharan R., Ha H.;
J. Biol. Chem. 0:0-0(2012).
Cited for: PHOSPHORYLATION AT THR-354 BY MELK, PHOSPHORYLATION AT SER-394 ANDSER-398 BY MAP3K5, AND MUTAGENESIS OF THR-354; SER-394 AND SER-398.
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Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures