Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0002129
UniProt IDO15530
Primary gene name(s)PDPK1
Synonym gene name(s)PDK1
Protein name3-phosphoinositide-dependent protein kinase 1
Protein functionSerine/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. {ECO:0000269|PubMed:10226025, ECO:0000269|PubMed:10480933, ECO:0000269|PubMed:10995762, ECO:0000269|PubMed:12167717, ECO:0000269|PubMed:14585963, ECO:0000269|PubMed:14604990, ECO:0000269|PubMed:16207722, ECO:0000269|PubMed:16251192, ECO:0000269|PubMed:17327236, ECO:0000269|PubMed:17371830, ECO:0000269|PubMed:18835241, ECO:0000269|PubMed:9094314, ECO:0000269|PubMed:9445476, ECO:0000269|PubMed:9707564, ECO:0000269|PubMed:9768361}.
Subcellular locationCytoplasm. 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 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.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: O15530
Gene Ontology
(Biological Process)
Complete annatation
actin cytoskeleton organization [GO:0030036];
activation of protein kinase B activity [GO:0032148];
calcium-mediated signaling [GO:0019722];
cell migration [GO:0016477];
cellular response to brain-derived neurotrophic factor stimulus [GO:1990416];
cellular response to epidermal growth factor stimulus [GO:0071364];
cellular response to insulin stimulus [GO:0032869];
epidermal growth factor receptor signaling pathway [GO:0007173];
extrinsic apoptotic signaling pathway [GO:0097191];
Fc-epsilon receptor signaling pathway [GO:0038095];
focal adhesion assembly [GO:0048041];
hyperosmotic response [GO:0006972];
intracellular signal transduction [GO:0035556];
negative regulation of cardiac muscle cell apoptotic process [GO:0010667];
negative regulation of neuron apoptotic process [GO:0043524];
negative regulation of protein kinase activity [GO:0006469];
negative regulation of toll-like receptor signaling pathway [GO:0034122];
negative regulation of transforming growth factor beta receptor signaling pathway [GO:0030512];
peptidyl-serine phosphorylation [GO:0018105];
peptidyl-threonine phosphorylation [GO:0018107];
phosphatidylinositol-mediated signaling [GO:0048015];
platelet activation [GO:0030168];
positive regulation of establishment of protein localization to plasma membrane [GO:0090004];
positive regulation of phospholipase activity [GO:0010518];
positive regulation of release of sequestered calcium ion into cytosol [GO:0051281];
protein autophosphorylation [GO:0046777];
protein phosphorylation [GO:0006468];
regulation of endothelial cell migration [GO:0010594];
regulation of I-kappaB kinase/NF-kappaB signaling [GO:0043122];
regulation of mast cell degranulation [GO:0043304];
regulation of transcription, DNA-templated [GO:0006355];
stimulatory C-type lectin receptor signaling pathway [GO:0002223];
T cell costimulation [GO:0031295];
T cell receptor signaling pathway [GO:0050852];
transcription, DNA-templated [GO:0006351];
type B pancreatic cell development [GO:0003323]
Gene Ontology
(Molecular Function)
Complete annatation
3-phosphoinositide-dependent protein kinase activity [GO:0004676];
ATP binding [GO:0005524];
kinase activity [GO:0016301];
phospholipase activator activity [GO:0016004];
phospholipase binding [GO:0043274];
protein serine/threonine kinase activity [GO:0004674]
Gene Ontology
(Cellular Component)
Complete annatation
cell projection [GO:0042995];
cytoplasm [GO:0005737];
cytoplasmic, membrane-bounded vesicle [GO:0016023];
cytosol [GO:0005829];
focal adhesion [GO:0005925];
neuronal postsynaptic density [GO:0097481];
nucleoplasm [GO:0005654];
plasma membrane [GO:0005886]
Protein-protein interaction111196
Phylogenetic treeO15530
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model

DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD30.2573738795594460.4320877468272620.553354279903178
AZA vs. DISU0.1544853838714220.541844976298150.94388010296314
AZA vs. IL7-0.01382870573177880.9426721443046770.999311006273513
AZA vs. SAHA-0.03714174076200060.8791641254615920.97315727227035
DISU vs. CD3-0.1154937716247790.7510139686656410.82669669663107
DISU vs. IL7-0.1774057739353890.4815376594625690.815232336082343
DISU vs. SAHA-0.1900380800855450.5169189087285320.834782609935845
DMSO vs. AZA0.01370376591783720.9348415777961361
DMSO vs. CD3-0.2565038665464020.4227444282195490.537135735572405
DMSO vs. DISU-0.1429188684086960.5584135403533750.924836638387915
DMSO vs. IL7-0.02010053790595930.9110095894842510.981734048116649
DMSO vs. SAHA-0.05679844069207880.8099125664351830.947685736703777
HIV vs. Mock in Activation0.2671171083353680.6682593717890780.999983755607037
HIV vs. Mock in Latency0.03348958610356790.8391525876494930.999834320637052
IL7 vs. CD3-0.264236085627610.4114215844466860.548759935075159
SAHA vs. CD3-0.3190290159738950.3664308728000890.483229817575084
SAHA vs. IL7-0.02673779968848040.9127824834759840.966891031836218
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) TRUE
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK 0.0881602 0.611715
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
1.047 1.105 1.24 1.395 1.225
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB00482 Celecoxib approved, investigational unknown inhibitor
DB01933 7-Hydroxystaurosporine experimental unknown unknown
DB01946 3-[1-(3-Aminopropyl)-1h-Indol-3-Yl]-4-(1-Methyl-1h-Indol-3-Yl)-1h-Pyrrole-2,5-Dione experimental unknown unknown
DB02010 Staurosporine experimental unknown unknown
DB04522 Phosphonoserine experimental unknown unknown
DB06932 10,11-dimethoxy-4-methyldibenzo[c,f]-2,7-naphthyridine-3,6-diamine experimental unknown unknown
DB07033 5-HYDROXY-3-[(1R)-1-(1H-PYRROL-2-YL)ETHYL]-2H-INDOL-2-ONE experimental unknown unknown
DB07132 1-{2-OXO-3-[(1R)-1-(1H-PYRROL-2-YL)ETHYL]-2H-INDOL-5-YL}UREA experimental unknown unknown
DB07300 2-(1H-imidazol-1-yl)-9-methoxy-8-(2-methoxyethoxy)benzo[c][2,7]naphthyridin-4-amine experimental unknown unknown
DB03777 Rbt205 Inhibitor experimental unknown unknown
DB07456 3-(1H-INDOL-3-YL)-4-(1-{2-[(2S)-1-METHYLPYRROLIDINYL]ETHYL}-1H-INDOL-3-YL)-1H-PYRROLE-2,5-DIONE experimental unknown unknown
DB07457 3-[1-(3-AMINOPROPYL)-1H-INDOL-3-YL]-4-(1H-INDOL-3-YL)-1H-PYRROLE-2,5-DIONE experimental unknown unknown
DB01863 Inositol 1,3,4,5-Tetrakisphosphate experimental unknown unknown

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1H1W X-ray 2.0Å A=71-359.
1OKY X-ray 2.3Å A=51-360.
1OKZ X-ray 2.5Å A=51-360.
1UU3 X-ray 1.7Å A=51-360.
1UU7 X-ray 1.9Å A=51-360.
1UU8 X-ray 2.5Å A=51-360.
1UU9 X-ray 1.9Å A=72-357.
1UVR X-ray 2.8Å A=71-359.
1W1D X-ray 1.5Å A=409-556.
1W1G X-ray 1.4Å A=409-556.
1W1H X-ray 1.4Å A/B/C/D=409-556.
1Z5M X-ray 2.1Å A=74-359.
2BIY X-ray 1.9Å A=51-360.
2PE0 X-ray 2.3Å A=74-359.
2PE1 X-ray 2.1Å A=74-359.
2PE2 X-ray 2.1Å A=74-359.
2R7B X-ray 2.7Å A=48-359.
2VKI X-ray 1.8Å A=409-556.
2XCH X-ray 2.0Å A=51-359.
2XCK X-ray 2.3Å A=51-359.
3H9O X-ray 2.3Å A=51-359.
3HRC X-ray 1.9Å A=50-359.
3HRF X-ray 1.9Å A=50-359.
3ION X-ray 2.4Å A=48-359.
3IOP X-ray 2.2Å A=48-359.
3NAX X-ray 1.7Å A=66-362.
3NAY X-ray 2.6Å A/B=66-362.
3NUN X-ray 2.2Å A=67-358.
3NUS X-ray 2.7Å A=73-358.
3NUU X-ray 1.9Å A=73-358.
3NUY X-ray 2.1Å A=73-358.
3ORX X-ray 2.2Å A/B/C/D/E/F/G/H=51-359.
3ORZ X-ray 2.0Å A/B/C/D=51-359.
3OTU X-ray 2.1Å A=51-359.
3PWY X-ray 3.5Å A=51-359.
3QC4 X-ray 1.8Å A/B=51-359.
3QCQ X-ray 2.5Å A=48-359.
3QCS X-ray 2.4Å A=48-359.
3QCX X-ray 2.3Å A=48-359.
3QCY X-ray 2.2Å A=48-359.
3QD0 X-ray 1.9Å A=48-359.
3QD3 X-ray 2.0Å A=48-359.
3QD4 X-ray 2.3Å A=48-359.
3RCJ X-ray 1.7Å A=50-359.
3RWP X-ray 1.9Å A=51-359.
3RWQ X-ray 2.5Å A=51-359.
3SC1 X-ray 2.7Å A=50-359.
4A06 X-ray 2.0Å A=50-359.
4A07 X-ray 1.8Å A=50-359.
4AW0 X-ray 1.4Å A=51-359.
4AW1 X-ray 1.6Å A=51-359.
4CT1 X-ray 1.8Å A=50-359.
4CT2 X-ray 1.2Å A=50-359.
4RQK X-ray 1.5Å A=50-359.
4RQV X-ray 1.5Å A=50-359.
4RRV X-ray 1.4Å A=50-359.
4XX9 X-ray 1.4Å A=50-359.
5ACK X-ray 1.2Å A=50-359.
5HKM X-ray 2.1Å A=51-359.
5HNG X-ray 3.0Å A=51-359.
5HO7 X-ray 3.0Å A=51-359.
5HO8 X-ray 2.7Å A=51-359.
5LVL X-ray 1.4Å A=50-359.
5LVM X-ray 1.2Å A=50-359.
5LVN X-ray 1.3Å A=50-359.
5LVO X-ray 1.0Å A=50-359.
5LVP X-ray 2.5Å A/B/C/D=50-359.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

HIV Partner Interaction Type PubMed
Tat induces phosphorylation of 21697490

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa01524 Platinum drug resistance - Homo sapiens (human)
hsa03320 PPAR signaling pathway - Homo sapiens (human)
hsa04068 FoxO signaling pathway - Homo sapiens (human)
hsa04071 Sphingolipid signaling pathway - Homo sapiens (human)
hsa04150 mTOR signaling pathway - Homo sapiens (human)
hsa04151 PI3K-Akt signaling pathway - Homo sapiens (human)
hsa04152 AMPK signaling pathway - Homo sapiens (human)
hsa04210 Apoptosis - Homo sapiens (human)
hsa04510 Focal adhesion - Homo sapiens (human)
hsa04660 T cell receptor signaling pathway - Homo sapiens (human)
hsa04664 Fc epsilon RI signaling pathway - Homo sapiens (human)
hsa04722 Neurotrophin signaling pathway - Homo sapiens (human)
hsa04910 Insulin signaling pathway - Homo sapiens (human)
hsa04919 Thyroid hormone signaling pathway - Homo sapiens (human)
hsa04931 Insulin resistance - Homo sapiens (human)
hsa04960 Aldosterone-regulated sodium reabsorption - Homo sapiens (human)
hsa05145 Toxoplasmosis - Homo sapiens (human)
hsa05160 Hepatitis C - Homo sapiens (human)
hsa05205 Proteoglycans in cancer - Homo sapiens (human)
hsa05213 Endometrial cancer - Homo sapiens (human)
hsa05215 Prostate cancer - Homo sapiens (human)
hsa05223 Non-small cell lung cancer - Homo sapiens (human)
hsa05231 Choline metabolism in cancer - Homo sapiens (human)