Gene/Proteome Database (LMPD)
LMPD ID
LMP012767
Gene ID
Species
Rattus norvegicus (Rat)
Gene Name
3-phosphoinositide dependent protein kinase-1
Gene Symbol
Alternate Names
3-phosphoinositide-dependent protein kinase 1; pkB kinase; protein kinase B kinase;
Chromosome
10
Map Location
10q12
EC Number
2.7.11.1
Summary
may catalyze the phosphorylation and activation of protein kinase B [RGD, Feb 2006]
Orthologs
Proteins
| 3-phosphoinositide-dependent protein kinase 1 | |
|---|---|
| Refseq ID | NP_112343 |
| Protein GI | 13592023 |
| UniProt ID | O55173 |
| mRNA ID | NM_031081 |
| Length | 559 |
| MARTTSQLYDAVPIQSSVVLCSCPSPSMVRSQTEPSSSPGIPSGVSRQGSTMDGTTAEARPSTNPLQQHPAQLPPQPRKKRPEDFKFGKILGEGSFSTVVLARELATSREYAIKILEKRHIIKENKVPYVTRERDVMSRLDHPFFVKLYFTFQDDEKLYFGLSYAKNGELLKYIRKIGSFDETCTRFYTAEIVSALEYLHGKGIIHRDLKPENILLNEDMHIQITDFGTAKVLSPDSKQARANSFVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNEYLIFQKIIKLEYDFPEKFFPKARDLVEKLLVLDATKRLGCEEMEGYGPLKAHPFFESITWENLHQQTPPKLTAYLPAMSEDDEDCYGNYDNLLSQFGCMQVSSSSSSHSLCAVDASLPQRSGSNIEQYIHDLDTNSFELDLQFSEDEKRLLLEKQAGGNPWHQFVENNLILKMGPVDKRKGLFARRRQLLLTEGPHLYYVDPVNKVLKGEIPWSQELRPEAKNFKTFFVHTPNRTYYLMDPSGNAHKWCRKIQEVWRQQYQSSPDAAVQ | |
Gene Information
Entrez Gene ID
Gene Name
3-phosphoinositide dependent protein kinase-1
Gene Symbol
Species
Rattus norvegicus
Gene Ontology (GO Annotations)
| GO ID | Source | Type | Description |
|---|---|---|---|
| GO:0030054 | IEA:UniProtKB-KW | C | cell junction |
| GO:0042995 | IEA:Ensembl | C | cell projection |
| GO:0016023 | IEA:Ensembl | C | cytoplasmic membrane-bounded vesicle |
| GO:0005829 | IDA:RGD | C | cytosol |
| GO:0005634 | IEA:UniProtKB-KW | C | nucleus |
| GO:0005886 | IDA:RGD | C | plasma membrane |
| GO:0004676 | IDA:RGD | F | 3-phosphoinositide-dependent protein kinase activity |
| GO:0005524 | IEA:UniProtKB-KW | F | ATP binding |
| GO:0005158 | IDA:RGD | F | insulin receptor binding |
| GO:0016004 | IEA:Ensembl | F | phospholipase activator activity |
| GO:0019901 | IDA:RGD | F | protein kinase binding |
| GO:0032148 | IEA:Ensembl | P | activation of protein kinase B activity |
| GO:0019722 | IEA:Ensembl | P | calcium-mediated signaling |
| GO:0016477 | IEA:Ensembl | P | cell migration |
| GO:0071364 | IEA:Ensembl | P | cellular response to epidermal growth factor stimulus |
| GO:0032869 | IEA:Ensembl | P | cellular response to insulin stimulus |
| GO:0007173 | IEA:Ensembl | P | epidermal growth factor receptor signaling pathway |
| GO:0097191 | IEA:Ensembl | P | extrinsic apoptotic signaling pathway |
| GO:0048041 | IMP:RGD | P | focal adhesion assembly |
| GO:0006972 | IEA:Ensembl | P | hyperosmotic response |
| GO:0010667 | IEA:Ensembl | P | negative regulation of cardiac muscle cell apoptotic process |
| GO:0006469 | IEA:Ensembl | P | negative regulation of protein kinase activity |
| GO:0034122 | IEA:Ensembl | P | negative regulation of toll-like receptor signaling pathway |
| GO:0030512 | IEA:Ensembl | P | negative regulation of transforming growth factor beta receptor signaling pathway |
| GO:0018107 | IEA:Ensembl | P | peptidyl-threonine phosphorylation |
| GO:0090004 | IEA:Ensembl | P | positive regulation of establishment of protein localization to plasma membrane |
| GO:0010518 | IEA:Ensembl | P | positive regulation of phospholipase activity |
| GO:0051281 | IEA:Ensembl | P | positive regulation of release of sequestered calcium ion into cytosol |
| GO:0043122 | IEA:Ensembl | P | regulation of I-kappaB kinase/NF-kappaB signaling |
| GO:0010594 | IEA:Ensembl | P | regulation of endothelial cell migration |
| GO:0043304 | IEA:Ensembl | P | regulation of mast cell degranulation |
| GO:0006355 | IEA:UniProtKB-KW | P | regulation of transcription, DNA-templated |
| GO:0006351 | IEA:UniProtKB-KW | P | transcription, DNA-templated |
| GO:0003323 | IEA:Ensembl | P | type B pancreatic cell development |
KEGG Pathway Links
| KEGG Pathway ID | Description |
|---|---|
| ko04152 | AMPK signaling pathway |
| rno04152 | AMPK signaling pathway |
| ko04960 | Aldosterone-regulated sodium reabsorption |
| rno04960 | Aldosterone-regulated sodium reabsorption |
| ko05213 | Endometrial cancer |
| rno05213 | Endometrial cancer |
| ko04664 | Fc epsilon RI signaling pathway |
| rno04664 | Fc epsilon RI signaling pathway |
| ko04510 | Focal adhesion |
| rno04510 | Focal adhesion |
| rno04068 | FoxO signaling pathway |
| ko05160 | Hepatitis C |
| rno05160 | Hepatitis C |
| ko04910 | Insulin signaling pathway |
| rno04910 | Insulin signaling pathway |
| ko04722 | Neurotrophin signaling pathway |
| rno04722 | Neurotrophin signaling pathway |
| ko05223 | Non-small cell lung cancer |
| rno05223 | Non-small cell lung cancer |
| ko04151 | PI3K-Akt signaling pathway |
| rno04151 | PI3K-Akt signaling pathway |
| ko03320 | PPAR signaling pathway |
| rno03320 | PPAR signaling pathway |
| ko05215 | Prostate cancer |
| rno05215 | Prostate cancer |
| ko05205 | Proteoglycans in cancer |
| rno05205 | Proteoglycans in cancer |
| ko04660 | T cell receptor signaling pathway |
| rno04660 | T cell receptor signaling pathway |
| rno04919 | Thyroid hormone signaling pathway |
| ko05145 | Toxoplasmosis |
| rno05145 | Toxoplasmosis |
| ko04150 | mTOR signaling pathway |
| rno04150 | mTOR signaling pathway |
REACTOME Pathway Links
| REACTOME Pathway ID | Description |
|---|---|
| 5953605 | Activation of NMDA receptor upon glutamate binding and postsynaptic events |
| 5953521 | Activation of PKB |
| 5953415 | Adaptive Immune System |
| 5953991 | CD28 co-stimulation |
| 5953990 | CD28 dependent PI3K/Akt signaling |
| 5954295 | CREB phosphorylation through the activation of Ras |
| 5954174 | CTLA4 inhibitory signaling |
| 5954570 | Constitutive PI3K/AKT Signaling in Cancer |
| 5953992 | Costimulation by the CD28 family |
| 5953408 | DAP12 interactions |
| 5953407 | DAP12 signaling |
| 5953253 | Disease |
| 5954035 | Downstream TCR signaling |
| 5953396 | Downstream signal transduction |
| 5953994 | Downstream signaling events of B Cell Receptor (BCR) |
| 5953399 | Downstream signaling of activated FGFR |
| 5954040 | FCERI mediated NF-kB activation |
| 5953417 | Fc epsilon receptor (FCERI) signaling |
| 5954002 | G beta:gamma signalling through PI3Kgamma |
| 5954003 | G-protein beta:gamma signalling |
| 5953884 | GAB1 signalosome |
| 5953642 | GPCR downstream signaling |
| 5953651 | GPVI-mediated activation cascade |
| 5953645 | Hemostasis |
| 5953430 | IGF1R signaling cascade |
| 5953428 | IRS-mediated signalling |
| 5953425 | IRS-related events |
| 5953429 | IRS-related events triggered by IGF1R |
| 5953410 | Immune System |
| 5953409 | Innate Immune System |
| 5953422 | Insulin receptor signalling cascade |
| 5954112 | Integrin alphaIIb beta3 signaling |
| 5953394 | NGF signalling via TRKA from the plasma membrane |
| 5953277 | Neuronal System |
| 5953606 | Neurotransmitter Receptor Binding And Downstream Transmission In The Postsynaptic Cell |
| 5953885 | PI-3K cascade |
| 5953432 | PI3K Cascade |
| 5953996 | PI3K events in ERBB2 signaling |
| 5953995 | PI3K events in ERBB4 signaling |
| 5953997 | PI3K/AKT Signaling in Cancer |
| 5953989 | PI3K/AKT activation |
| 5953993 | PIP3 activates AKT signaling |
| 5954113 | Platelet Aggregation (Plug Formation) |
| 5953644 | Platelet activation, signaling and aggregation |
| 5953604 | Post NMDA receptor activation events |
| 5954298 | RSK activation |
| 5953998 | Role of LAT2/NTAL/LAB on calcium mobilization |
| 5953381 | Signal Transduction |
| 5953403 | Signaling by EGFR |
| 5953404 | Signaling by EGFR in Cancer |
| 5953406 | Signaling by ERBB2 |
| 5953540 | Signaling by ERBB4 |
| 5953400 | Signaling by FGFR |
| 5953401 | Signaling by FGFR in disease |
| 5953391 | Signaling by GPCR |
| 5953423 | Signaling by Insulin receptor |
| 5953397 | Signaling by PDGF |
| 5953541 | Signaling by SCF-KIT |
| 5953431 | Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) |
| 5953420 | Signaling by VEGF |
| 5953414 | Signaling by the B Cell Receptor (BCR) |
| 5953395 | Signalling by NGF |
| 5954036 | TCR signaling |
| 5953276 | Transmission across Chemical Synapses |
| 5953419 | VEGFA-VEGFR2 Pathway |
| 5953418 | VEGFR2 mediated cell proliferation |
| 5953999 | VEGFR2 mediated vascular permeability |
Domain Information
InterPro Annotations
| Accession | Description |
|---|---|
| IPR011993 | Pleckstrin homology-like domain |
| IPR000719 | Protein kinase domain |
| IPR017441 | Protein kinase, ATP binding site |
| IPR011009 | Protein kinase-like domain |
| IPR008271 | Serine/threonine-protein kinase, active site |
| IPR002290 | Serine/threonine/dual specificity protein kinase, catalytic domain |
UniProt Annotations
Entry Information
Gene Name
3-phosphoinositide dependent protein kinase-1
Protein Entry
PDPK1_RAT
UniProt ID
Species
Rat
Comments
| Comment Type | Description |
|---|---|
| Catalytic Activity | ATP + a protein = ADP + a phosphoprotein. |
| Domain | The PH domain plays a pivotal role in the localization and nuclear import of PDPK1 and is also essential for its homodimerization |
| 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-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) |
| 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 (By similarity) |
| Ptm | Monoubiquitinated in the kinase domain, deubiquitinated by USP4 |
| 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. 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) |
| Similarity | Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PDPK1 subfamily |
| Similarity | Contains 1 PH domain |
| Similarity | Contains 1 protein kinase domain |
| Subcellular Location | Cytoplasm . Nucleus {ECO:0000250}. 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-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-244 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) |
| Subunit | 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-244 phosphorylated form interacts with YWHAH and YWHAQ. Binds INSR in response to insulin. Interacts (via PH domain) with SMAD3, SMAD4 and SMAD7 (By similarity). 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. {ECO:0000250, ECO:0000269|PubMed:11781095}. |
Identical and Related Proteins
Unique RefSeq proteins for LMP012767 (as displayed in Record Overview)
| Protein GI | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| 13592023 | RefSeq | NP_112343 | 559 | 3-phosphoinositide-dependent protein kinase 1 |
Identical Sequences to LMP012767 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:13592023 | EMBL | CAA75758.1 | 559 | PkB kinase [Rattus norvegicus] |
Related Sequences to LMP012767 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:13592023 | EMBL | CAA75758.1 | 559 | PkB kinase [Rattus norvegicus] |
| GI:13592023 | GenBank | EDM03805.1 | 559 | 3-phosphoinositide dependent protein kinase-1, isoform CRA_a [Rattus norvegicus] |
| GI:13592023 | SwissProt | O55173.2 | 559 | RecName: Full=3-phosphoinositide-dependent protein kinase 1; AltName: Full=Protein kinase B kinase; Short=PkB kinase [Rattus norvegicus] |