Pdpk1
entrez
18607
canonical
uniprot
Q9Z2A0
canonical
ensembl
ENSMUSG00000024122
resolver
ensp
ENSMUSP00000061942
resolver
ensp
ENSMUSP00000099991
resolver
ensp
ENSMUSP00000111070
resolver
enst
ENSMUST00000052462
resolver
enst
ENSMUST00000102927
resolver
enst
ENSMUST00000115411
resolver
genesymbol
Pdpk1
resolver
genesymbol_syn
Pdk1
resolver
uniprot
A6H6U3
resolver
uniprot
F2Z3X6
resolver
uniprot
F6UW60
resolver
uniprot
Q3TRL2
resolver
uniprot
Q3UGN6
resolver
uniprot
Q3UHZ0
resolver
uniprot
Q9R1D8
resolver
uniprot
Q9R215
resolver
uniprot_entry
F2Z3X6_MOUSE
resolver
uniprot_entry
F6UW60_MOUSE
resolver
uniprot_entry
PDPK1_MOUSE
resolver
uniprot_entry
Q3TRL2_MOUSE
resolver
uniprot_entry
Q3UGN6_MOUSE
resolver
uniprot_entry
Q3UHZ0_MOUSE
resolver
uniprot_sec
A6H6U3
resolver
uniprot_sec
Q9R1D8
resolver
uniprot_sec
Q9R215
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-376 and Tyr-379 residues. The 14-3-3 protein YWHAQ acts as a negative regulator by association with the residues surrounding the Ser-244 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-376 and Tyr-379 by INSR in response to insulin (By similarity). {ECO:0000250}.
uniprot
proteins
amino_acid_sequence
MARTTSQLYDAVPIQSSVVLCSCPSPSMVRSQTEPGSSPGIPSGVSRQGSTMDGTTAEARPSTNPLQQHPAQLPPQPRKKRPEDFKFGKILGEGSFSTVVLARELATSREYAIKILEKRHIIKENKVPYVTRERDVMSRLDHPFFVKLYFTFQDDEKLYFGLSYAKNGELLKYIRKIGSFDETCTRFYTAEIVSALEYLHGKGIIHRDLKPENILLNEDMHIQITDFGTAKVLSPESKQARANSFVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNEYLIFQKIIKLEYHFPEKFFPKARDLVEKLLVLDATKRLGCEEMEGYGPLKAHPFFETITWENLHQQTPPKLTAYLPAMSEDDEDCYGNYDNLLSQFGFMQVSSSSSSHSLSTVETSLPQRSGSNIEQYIHDLDTNSFELDLQFSEDEKRLLLEKQAGGNPWHQFVENNLILKMGPVDKRKGLFARRRQLLLTEGPHLYYVDPVNKVLKGEIPWSQELRPEAKNFKTFFVHTPNRTYYLMDPSGNAHKWCRKIQEVWRQQYQSNPDAAVQ
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:10075713, PubMed:16150867, PubMed:16336268, PubMed:19047061, PubMed:19635472, PubMed:21063107). 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:10075713, PubMed:10792047, PubMed:16336268, PubMed:19047061). 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 (By similarity). 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 (By similarity). Activates PPARG transcriptional activity and promotes adipocyte differentiation (PubMed:16150867). Activates the NF-kappa-B pathway via phosphorylation of IKKB (By similarity). The tyrosine phosphorylated form is crucial for the regulation of focal adhesions by angiotensin II (By similarity). Controls proliferation, survival, and growth of developing pancreatic cells (PubMed:19635472). Participates in the regulation of Ca(2+) entry and Ca(2+)-activated K(+) channels of mast cells (PubMed:21063107). 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 (PubMed:19429709). 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 (PubMed:17599070). Provides negative feedback inhibition to toll-like receptor-mediated NF-kappa-B activation in macrophages (PubMed:20584979). {ECO:0000250|UniProtKB:O15530, ECO:0000269|PubMed:10075713, ECO:0000269|PubMed:10792047, ECO:0000269|PubMed:16150867, ECO:0000269|PubMed:16336268, ECO:0000269|PubMed:17371830, ECO:0000269|PubMed:17599070, ECO:0000269|PubMed:19047061, ECO:0000269|PubMed:19429709, ECO:0000269|PubMed:19635472, ECO:0000269|PubMed:20584979, ECO:0000269|PubMed:21063107}.
uniprot
proteins
mass_dalton
63759
uniprot
proteins
post_translational_modification
PTM: Phosphorylation on Ser-244 in the activation loop is required for full activity. PDPK1 itself can autophosphorylate Ser-244, 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-376 and Tyr-379 by INSR in response to insulin. Palmitate negatively regulates autophosphorylation at Ser-244 and palmitate-induced phosphorylation at Ser-532 and Ser-504 by PKC/PRKCQ negatively regulates its ability to phosphorylate PKB/AKT1. Phosphorylation at Thr-357 by MELK partially inhibits kinase activity, the inhibition is cooperatively enhanced by phosphorylation at Ser-397 and Ser-401 by MAP3K5 (By similarity). {ECO:0000250}.; PTM: Monoubiquitinated in the kinase domain, deubiquitinated by USP4. {ECO:0000250}.
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
10075713
uniprot
proteins
pubmed
10792047
uniprot
proteins
pubmed
15345747
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16150867
uniprot
proteins
pubmed
16336268
uniprot
proteins
pubmed
17242355
uniprot
proteins
pubmed
17371830
uniprot
proteins
pubmed
17599070
uniprot
proteins
pubmed
19047061
uniprot
proteins
pubmed
19429709
uniprot
proteins
pubmed
19635472
uniprot
proteins
pubmed
20584979
uniprot
proteins
pubmed
21063107
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
23806337
uniprot
proteins
sequence_length
559
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17371830}. Nucleus {ECO:0000250}. Cell membrane {ECO:0000269|PubMed:17371830}; Peripheral membrane protein {ECO:0000269|PubMed:17371830}. Cell junction, focal adhesion {ECO:0000250}. 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-244 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 (By similarity). {ECO:0000250}.
uniprot
proteins