PDPK1
entrez
5170
canonical
uniprot
O15530
canonical
ensembl
ENSG00000140992
resolver
ensp
ENSP00000268673
resolver
ensp
ENSP00000344220
resolver
ensp
ENSP00000373876
resolver
ensp
ENSP00000395357
resolver
ensp
ENSP00000663418
resolver
enst
ENST00000389224
resolver
genesymbol
PDPK1
resolver
genesymbol_syn
PDK1
resolver
hgnc
HGNC:8816
resolver
uniprot
E9PER6
resolver
uniprot
H0Y4Z0
resolver
uniprot
Q59EH6
resolver
uniprot
Q6FI20
resolver
uniprot
Q8IV52
resolver
uniprot
Q9BRD5
resolver
uniprot_entry
E9PER6_HUMAN
resolver
uniprot_entry
PDPK1_HUMAN
resolver
uniprot_sec
H0Y4Z0
resolver
uniprot_sec
Q59EH6
resolver
uniprot_sec
Q6FI20
resolver
uniprot_sec
Q8IV52
resolver
uniprot_sec
Q9BRD5
resolver
activity_regulation
ACTIVITY 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. {ECO:0000269|PubMed:12177059, ECO:0000269|PubMed:16251192, ECO:0000269|PubMed:18616680, ECO:0000269|PubMed:20978239}.
uniprot
proteins
amino_acid_sequence
MARTTSQLYDAVPIQSSVVLCSCPSPSMVRTQTESSTPPGIPGGSRQGPAMDGTAAEPRPGAGSLQHAQPPPQPRKKRPEDFKFGKILGEGSFSTVVLARELATSREYAIKILEKRHIIKENKVPYVTRERDVMSRLDHPFFVKLYFTFQDDEKLYFGLSYAKNGELLKYIRKIGSFDETCTRFYTAEIVSALEYLHGKGIIHRDLKPENILLNEDMHIQITDFGTAKVLSPESKQARANSFVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNEYLIFQKIIKLEYDFPEKFFPKARDLVEKLLVLDATKRLGCEEMEGYGPLKAHPFFESVTWENLHQQTPPKLTAYLPAMSEDDEDCYGNYDNLLSQFGCMQVSSSSSSHSLSASDTGLPQRSGSNIEQYIHDLDSNSFELDLQFSEDEKRLLLEKQAGGNPWHQFVENNLILKMGPVDKRKGLFARRRQLLLTEGPHLYYVDPVNKVLKGEIPWSQELRPEAKNFKTFFVHTPNRTYYLMDPSGNAHKWCRKIQEVWRQRYQSHPDAAVQ
uniprot
proteins
ec_number
2.7.11.1
uniprot
proteins
function
FUNCTION: Serine/threonine kinase which acts as a master kinase, phosphorylating and activating a subgroup of the AGC family of protein kinases (PubMed:10226025, PubMed:10480933, PubMed:10995762, PubMed:12167717, PubMed:14585963, PubMed:14604990, PubMed:16207722, PubMed:16251192, PubMed:17327236, PubMed:17371830, PubMed:18835241, PubMed:9094314, PubMed:9368760, PubMed:9445476, PubMed:9445477, PubMed:9707564, PubMed:9768361). 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), TSSK3, protein kinase PKN (PKN1 and PKN2) (PubMed:10226025, PubMed:10480933, PubMed:10995762, PubMed:12167717, PubMed:14585963, PubMed:14604990, PubMed:16207722, PubMed:16251192, PubMed:17327236, PubMed:17371830, PubMed:18835241, PubMed:9094314, PubMed:9368760, PubMed:9445476, PubMed:9707564, PubMed:9768361). 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 (PubMed:10226025, PubMed:12167717, PubMed:9094314). 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 (PubMed:17327236). Activates PPARG transcriptional activity and promotes adipocyte differentiation (By similarity). Activates the NF-kappa-B pathway via phosphorylation of IKKB (PubMed:16207722). The tyrosine phosphorylated form is crucial for the regulation of focal adhesions by angiotensin II (PubMed:14585963). Controls proliferation, survival, and growth of developing pancreatic cells (By similarity). Participates in the regulation of Ca(2+) entry and Ca(2+)-activated K(+) channels of mast cells (By similarity). Essential for the motility of vascular endothelial cells (ECs) and is involved in the regulation of their chemotaxis (PubMed:17371830). Plays a critical role in cardiac homeostasis by serving as a dual effector for cell survival and beta-adrenergic response (By similarity). 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 (By similarity). Provides negative feedback inhibition to toll-like receptor-mediated NF-kappa-B activation in macrophages (By similarity). {ECO:0000250|UniProtKB:Q9Z2A0, 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:9368760, ECO:0000269|PubMed:9445476, ECO:0000269|PubMed:9445477, ECO:0000269|PubMed:9707564, ECO:0000269|PubMed:9768361}.; FUNCTION: [Isoform 3]: Catalytically inactive. {ECO:0000269|PubMed:9445477}.
uniprot
proteins
mass_dalton
63152
uniprot
proteins
mutagenesis
MUTAGEN 9; /note="Y->F: Slight reduction in pervanadate-stimulated tyrosine phosphorylation."; /evidence="ECO:0000269|PubMed:11481331"; MUTAGEN 25; /note="S->A: No effect."; /evidence="ECO:0000269|PubMed:10455013"; MUTAGEN 241; /note="S->A: No activation."; /evidence="ECO:0000269|PubMed:10455013"; MUTAGEN 277; /note="A->V: 3-fold increase in kinase activity."; /evidence="ECO:0000269|PubMed:10364160"; MUTAGEN 354; /note="T->A: Abolishes phosphorylation by MELK."; /evidence="ECO:0000269|PubMed:22544756"; MUTAGEN 373; /note="Y->F: Reduction in basal activity."; /evidence="ECO:0000269|PubMed:11481331"; MUTAGEN 376; /note="Y->F: Reduction in basal activity."; /evidence="ECO:0000269|PubMed:11481331"; MUTAGEN 393; /note="S->A: No effect."; /evidence="ECO:0000269|PubMed:10455013"; MUTAGEN 394; /note="S->A: Abolishes phosphorylation by MAP3K5; when associated with A-398."; /evidence="ECO:0000269|PubMed:22544756"; MUTAGEN 396; /note="S->A: No effect."; /evidence="ECO:0000269|PubMed:10455013"; MUTAGEN 398; /note="S->A: Abolishes phosphorylation by MAP3K5; when associated with A-394."; /evidence="ECO:0000269|PubMed:22544756"; MUTAGEN 410; /note="S->A: No effect."; /evidence="ECO:0000269|PubMed:10455013"; MUTAGEN 474; /note="R->A: No PDGF-dependent translocation to the membrane."; /evidence="ECO:0000269|PubMed:9637919"; MUTAGEN 513; /note="T->E: Enhanced kinase activity towards PKB."; /evidence="ECO:0000269|PubMed:20978239
uniprot
proteins
post_translational_modification
PTM: 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. {ECO:0000250, ECO:0000269|PubMed:10455013, ECO:0000269|PubMed:11481331, ECO:0000269|PubMed:14585963, ECO:0000269|PubMed:15743829, ECO:0000269|PubMed:16314505, ECO:0000269|PubMed:16780920, ECO:0000269|PubMed:22544756, ECO:0000269|Ref.8}.; PTM: Autophosphorylated; autophosphorylation is inhibited by the apoptotic C-terminus cleavage product of PKN2. {ECO:0000250}.; PTM: Monoubiquitinated in the kinase domain, deubiquitinated by USP4.
uniprot
proteins
protein_family
AGC Ser/Thr protein kinase family
uniprot
proteins
protein_family
PDPK1 subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
pubmed
10226025
uniprot
proteins
pubmed
10364160
uniprot
proteins
pubmed
10455013
uniprot
proteins
pubmed
10480933
uniprot
proteins
pubmed
10995762
uniprot
proteins
pubmed
11481331
uniprot
proteins
pubmed
12167717
uniprot
proteins
pubmed
12169624
uniprot
proteins
pubmed
12177059
uniprot
proteins
pubmed
14585963
uniprot
proteins
pubmed
14604990
uniprot
proteins
pubmed
15209375
uniprot
proteins
pubmed
15210700
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15616553
uniprot
proteins
pubmed
15741170
uniprot
proteins
pubmed
15743829
uniprot
proteins
pubmed
15772071
uniprot
proteins
pubmed
16207722
uniprot
proteins
pubmed
16251192
uniprot
proteins
pubmed
16314505
uniprot
proteins
pubmed
16780920
uniprot
proteins
pubmed
17327236
uniprot
proteins
pubmed
17371830
uniprot
proteins
pubmed
18024423
uniprot
proteins
pubmed
18616680
uniprot
proteins
pubmed
18802401
uniprot
proteins
pubmed
18835241
uniprot
proteins
pubmed
19276999
uniprot
proteins
pubmed
19591923
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20978239
uniprot
proteins
pubmed
22347420
uniprot
proteins
pubmed
22544756
uniprot
proteins
pubmed
22999883
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
9094314
uniprot
proteins
pubmed
9368760
uniprot
proteins
pubmed
9445476
uniprot
proteins
pubmed
9445477
uniprot
proteins
pubmed
9637919
uniprot
proteins
pubmed
9707564
uniprot
proteins
pubmed
9768361
uniprot
proteins
sequence_length
556
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: 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 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.
uniprot
proteins