Gene/Proteome Database (LMPD)

LMPD ID
LMP000506
Gene ID
5170
Species
Homo sapiens (Human)
Gene Name
3-phosphoinositide dependent protein kinase 1
Gene Symbol
PDPK1
Synonyms
PDK1; PDPK2; PRO0461
Alternate Names
3-phosphoinositide-dependent protein kinase 1; PkB kinase like gene 1; 3-phosphoinositide dependent protein kinase-1; 3-phosphoinositide-dependent protein kinase 2 pseudogene
Chromosome
16
Map Location
16p13.3
EC Number
2.7.11.1

Proteins

3-phosphoinositide-dependent protein kinase 1 isoform 1
Refseq ID NP_002604
Protein GI 4505695
UniProt ID O15530
mRNA ID NM_002613
Length 556
RefSeq Status VALIDATED
MARTTSQLYDAVPIQSSVVLCSCPSPSMVRTQTESSTPPGIPGGSRQGPAMDGTAAEPRPGAGSLQHAQPPPQPRKKRPEDFKFGKILGEGSFSTVVLARELATSREYAIKILEKRHIIKENKVPYVTRERDVMSRLDHPFFVKLYFTFQDDEKLYFGLSYAKNGELLKYIRKIGSFDETCTRFYTAEIVSALEYLHGKGIIHRDLKPENILLNEDMHIQITDFGTAKVLSPESKQARANSFVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNEYLIFQKIIKLEYDFPEKFFPKARDLVEKLLVLDATKRLGCEEMEGYGPLKAHPFFESVTWENLHQQTPPKLTAYLPAMSEDDEDCYGNYDNLLSQFGCMQVSSSSSSHSLSASDTGLPQRSGSNIEQYIHDLDSNSFELDLQFSEDEKRLLLEKQAGGNPWHQFVENNLILKMGPVDKRKGLFARRRQLLLTEGPHLYYVDPVNKVLKGEIPWSQELRPEAKNFKTFFVHTPNRTYYLMDPSGNAHKWCRKIQEVWRQRYQSHPDAAVQ
3-phosphoinositide-dependent protein kinase 1 isoform 2
Refseq ID NP_112558
Protein GI 47680169
UniProt ID O15530
mRNA ID NM_031268
Length 429
RefSeq Status VALIDATED
MARTTSQLYDAVPIQSSVVLCSCPSPSMVRTQTESSTPPGIPGGSRQGPAMDGTAAEPRPGAGSLQHAQPPPQPRKKRPEDFKFGKILGEGSFSTVVLARELATSREYATRANSFVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNEYLIFQKIIKLEYDFPEKFFPKARDLVEKLLVLDATKRLGCEEMEGYGPLKAHPFFESVTWENLHQQTPPKLTAYLPAMSEDDEDCYGNYDNLLSQFGCMQVSSSSSSHSLSASDTGLPQRSGSNIEQYIHDLDSNSFELDLQFSEDEKRLLLEKQAGGNPWHQFVENNLILKMGPVDKRKGLFARRRQLLLTEGPHLYYVDPVNKVLKGEIPWSQELRPEAKNFKTFFVHTPNRTYYLMDPSGNAHKWCRKIQEVWRQRYQSHPDAAVQ
3-phosphoinositide-dependent protein kinase 1 isoform 3
Refseq ID NP_001248745
Protein GI 387849239
UniProt ID O15530
mRNA ID NM_001261816
Length 454
RefSeq Status VALIDATED
MARTTSQLYDAVPIQSSVVLCSCPSPSMVRTQTESSTPPGIPGGSRQGPAMDGTAAEPRPGAGSLQHAQPPPQPRKKRPEDFKFGKILGEGSFSTVVLARELATSREYAIKILEKRHIIKENKVPYVTRERDVMSRLDHPFFVKLYFTFQDDEKLYFGLSYAKNGELLKYIRKIGSFDETCTRFYTAEIVSALEYLHGKGIIHRDLKPENILLNEDMHIQITDFGTAKVLSPESKQARANSFVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNEYLIFQKIIKLEYDFPEKFFPKARDLVEKLLVLDATKRLGCEEMEGYGPLKAHPFFESVTWENLHQQTPPKLTAYLPAMSEDDEDCYGNYDNLLSQFGCMQVSSSSSSHSLSASDTGLPQRSGSNIEQYIHDLDSNSFELDLQFSEDEKRLLLEKQAGGNPCLTGRII

Gene Information

Entrez Gene ID
5170
Gene Name
3-phosphoinositide dependent protein kinase 1
Gene Symbol
PDPK1
Species
Homo sapiens

Gene Ontology (GO Annotations)

GO ID Source Type Description
GO:0030054 IEA:UniProtKB-KW C cell junction
GO:0042995 IDA:BHF-UCL C cell projection
GO:0005737 IDA:UniProtKB C cytoplasm
GO:0016023 IEA:Ensembl C cytoplasmic membrane-bounded vesicle
GO:0005829 TAS:Reactome C cytosol
GO:0005654 TAS:Reactome C nucleoplasm
GO:0005886 IDA:UniProtKB C plasma membrane
GO:0004676 IDA:BHF-UCL F 3-phosphoinositide-dependent protein kinase activity
GO:0005524 IEA:UniProtKB-KW F ATP binding
GO:0016301 EXP:Reactome F kinase activity
GO:0016004 IMP:BHF-UCL F phospholipase activator activity
GO:0043274 IPI:BHF-UCL F phospholipase binding
GO:0004674 IDA:BHF-UCL F protein serine/threonine kinase activity
GO:0038095 TAS:Reactome P Fc-epsilon receptor signaling pathway
GO:0031295 TAS:Reactome P T cell costimulation
GO:0050852 TAS:Reactome P T cell receptor signaling pathway
GO:0030036 TAS:ProtInc P actin cytoskeleton organization
GO:0032148 IDA:BHF-UCL P activation of protein kinase B activity
GO:0007596 TAS:Reactome P blood coagulation
GO:0019722 IMP:BHF-UCL P calcium-mediated signaling
GO:0016477 IMP:BHF-UCL P cell migration
GO:0071364 IMP:BHF-UCL P cellular response to epidermal growth factor stimulus
GO:0032869 IMP:BHF-UCL P cellular response to insulin stimulus
GO:0007173 IMP:BHF-UCL P epidermal growth factor receptor signaling pathway
GO:0097191 IMP:UniProtKB P extrinsic apoptotic signaling pathway
GO:0008543 TAS:Reactome P fibroblast growth factor receptor signaling pathway
GO:0048041 IEA:Ensembl P focal adhesion assembly
GO:0006972 IEA:Ensembl P hyperosmotic response
GO:0045087 TAS:Reactome P innate immune response
GO:0008286 TAS:Reactome P insulin receptor signaling pathway
GO:0035556 IDA:MGI P intracellular signal transduction
GO:0010667 IEA:Ensembl P negative regulation of cardiac muscle cell apoptotic process
GO:0006469 IDA:BHF-UCL P negative regulation of protein kinase activity
GO:0034122 IEA:Ensembl P negative regulation of toll-like receptor signaling pathway
GO:0030512 IDA:UniProtKB P negative regulation of transforming growth factor beta receptor signaling pathway
GO:0048011 TAS:Reactome P neurotrophin TRK receptor signaling pathway
GO:0018107 IDA:BHF-UCL P peptidyl-threonine phosphorylation
GO:0048015 TAS:Reactome P phosphatidylinositol-mediated signaling
GO:0030168 TAS:Reactome P platelet activation
GO:0090004 IMP:BHF-UCL P positive regulation of establishment of protein localization to plasma membrane
GO:0010518 IMP:BHF-UCL P positive regulation of phospholipase activity
GO:0051281 IDA:BHF-UCL P positive regulation of release of sequestered calcium ion into cytosol
GO:0046777 TAS:UniProtKB P protein autophosphorylation
GO:0006468 IDA:UniProtKB P protein phosphorylation
GO:0043122 IMP:UniProtKB 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:0007268 TAS:Reactome P synaptic transmission
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
hsa04152 AMPK signaling pathway
hsa04068 FoxO signaling pathway
hsa05205 Proteoglycans in cancer
hsa04919 Thyroid hormone signaling pathway

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_HUMAN
UniProt ID
O15530
Species
Human

Comments

Comment Type Description
Alternative Products Event=Alternative splicing; Named isoforms=5; Name=1; IsoId=O15530-1; Sequence=Displayed; Name=2; IsoId=O15530-2; Sequence=VSP_004894; Name=3; IsoId=O15530-3; Sequence=VSP_004895; Name=4; IsoId=O15530-4; Sequence=VSP_041902; Name=5; IsoId=O15530-5; Sequence=VSP_044796; Note=No experimental confirmation available.;
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-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
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. {ECO
Induction Stimulated by insulin, and the oxidants hydrogen peroxide and peroxovanadate.
Interaction P31749:AKT1; NbExp=3; IntAct=EBI-717097, EBI-296087; Q00005:PPP2R2B; NbExp=8; IntAct=EBI-717097, EBI-1052159; Q8IUH5:ZDHHC17; NbExp=3; IntAct=EBI-9087775, EBI-524753;
Ptm Autophosphorylated; autophosphorylation is inhibited by the apoptotic C-terminus cleavage product of PKN2.
Ptm Monoubiquitinated in the kinase domain, deubiquitinated by USP4.
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
Sequence Caution Sequence=BAD93072.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence= ;
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. 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.
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-241 phosphorylated form interacts with YWHAH and YWHAQ. Binds INSR in response to insulin. Interacts (via PH domain) with SMAD3, SMAD4 and SMAD7. 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
Tissue Specificity Appears to be expressed ubiquitously. The Tyr- 9 phosphorylated form is markedly increased in diseased tissue compared with normal tissue from lung, liver, colon and breast.

Identical and Related Proteins

Unique RefSeq proteins for LMP000506 (as displayed in Record Overview)

Protein GI Database Accession Length Protein Name
4505695 RefSeq NP_002604 556 3-phosphoinositide-dependent protein kinase 1 isoform 1
47680169 RefSeq NP_112558 429 3-phosphoinositide-dependent protein kinase 1 isoform 2
387849239 RefSeq NP_001248745 454 3-phosphoinositide-dependent protein kinase 1 isoform 3

Identical Sequences to LMP000506 proteins

Reference Database Accession Length Protein Name
GI:4505695 DBBJ BAG72895.1 556 3-phosphoinositide dependent protein kinase-1, partial [synthetic construct]
GI:47680169 GenBank AAH06339.2 429 3-phosphoinositide dependent protein kinase-1 [Homo sapiens]
GI:4505695 GenBank ACC27063.1 556 Sequence 1 from patent US 7344870
GI:47680169 GenBank ACE87795.1 429 3-phosphoinositide dependent protein kinase-1 protein [synthetic construct]
GI:47680169 GenBank ACT64575.1 429 3-phosphoinositide dependent protein kinase-1 protein, partial [synthetic construct]
GI:4505695 GenBank ADS40066.1 556 Sequence 3 from patent US 7792665
GI:4505695 GenBank ADS40174.1 556 Sequence 117 from patent US 7792665
GI:4505695 GenBank ADT53242.1 556 Sequence 1 from patent US 7842488
GI:4505695 GenBank AHD73263.1 556 Sequence 10331 from patent US 8586006
GI:47680169 GenBank AHD73264.1 429 Sequence 10332 from patent US 8586006
GI:47680169 GenBank AIC49361.1 429 PDPK1, partial [synthetic construct]
GI:47680169 GenBank AIC62546.1 429 PDPK1, partial [synthetic construct]

Related Sequences to LMP000506 proteins

Reference Database Accession Length Protein Name
GI:387849239 DBBJ BAD93072.1 492 3-phosphoinositide dependent protein kinase-1 variant, partial [Homo sapiens]
GI:387849239 EMBL CAA75341.1 556 PkB kinase [Homo sapiens]
GI:47680169 EMBL CBY20845.1 709 unnamed protein product [Oikopleura dioica]
GI:47680169 EMBL CBY24031.1 783 unnamed protein product [Oikopleura dioica]
GI:387849239 GenBank AAE29046.1 556 Sequence 4 from patent US 5962232
GI:4505695 GenBank AAS31681.1 556 Sequence 2 from patent US 6682920
GI:4505695 GenBank AAX29847.1 557 3-phosphoinositide dependent protein kinase-1, partial [synthetic construct]
GI:4505695 GenBank AAX43258.1 557 3-phosphoinositide dependent protein kinase-1, partial [synthetic construct]
GI:387849239 GenBank ABM83223.1 556 3-phosphoinositide dependent protein kinase-1 [synthetic construct]
GI:387849239 GenBank ABM86422.1 556 3-phosphoinositide dependent protein kinase-1, partial [synthetic construct]
GI:4505695 GenBank JAA10183.1 556 3-phosphoinositide dependent protein kinase-1 [Pan troglodytes]
GI:4505695 GenBank JAA16678.1 556 3-phosphoinositide dependent protein kinase-1 [Pan troglodytes]
GI:4505695 GenBank JAA29491.1 556 3-phosphoinositide dependent protein kinase-1 [Pan troglodytes]
GI:387849239 RefSeq NP_002604.1 556 3-phosphoinositide-dependent protein kinase 1 isoform 1 [Homo sapiens]
GI:47680169 RefSeq XP_004270330.1 432 PREDICTED: 3-phosphoinositide-dependent protein kinase 1 isoform 2 [Orcinus orca]
GI:47680169 RefSeq XP_007453585.1 431 PREDICTED: 3-phosphoinositide-dependent protein kinase 1 isoform X2 [Lipotes vexillifer]
GI:47680169 RefSeq XP_007613883.1 647 PREDICTED: beta-adrenergic receptor kinase 1 isoform X4 [Cricetulus griseus]
GI:47680169 RefSeq XP_008144654.1 431 PREDICTED: 3-phosphoinositide-dependent protein kinase 1 isoform X2 [Eptesicus fuscus]