Q9Z2A0

SS
Gene name
Pdpk1 (Pdk1)
Protein name
3-phosphoinositide-dependent protein kinase 1
Names
mPDK1
Species
Mus musculus (Mouse)
KEGG Pathway
mmu:18607
EC number
2.7.11.1: Protein-serine/threonine kinases
Protein Class

Descriptions

3-Phosphoinositide-dependent protein kinase-1 (PDPK1) plays a central role in activating the protein kinase A, G, and C subfamily. In particular, PDK1 plays an important role in regulating the Akt survival pathway. Human PDPK1 (O15530) forms a homodimer via its PH domain, which is an autoinhibited conformation. The ATP-binding site is buried in the structure and the PIF pocket in the kinase domain of one monomer is not accessible because of its occupancy by the αG helix of the other monomer. Thus, though the PH domain in PDPK1 does not mediate intramolecular interactions, it mediates the homodimerization by PH-PH interaction and results in autoinhibition. Deletion of the PH domain increases the interaction between PDPK1 and PKB.

Autoinhibitory domains (AIDs)

462-553 (PH domain) SS

Target domain

85-345 (Protein kinase domain)

Relief mechanism

PTM, Ligand binding

Assay

Accessory elements

225-250 (Activation loop from InterPro)

Target domain

85-345 (Protein kinase domain)

Relief mechanism

Assay

References

Autoinhibited structure

Activated structure

1 structures for Q9Z2A0

Entry ID Method Resolution Chain Position Source
AF-Q9Z2A0-F1 Predicted AlphaFoldDB

6 variants for Q9Z2A0

Variant ID(s) Position Change Description Diseaes Association Provenance
rs248533077 29 V>M No Ensembl
rs230000791 60 R>G No Ensembl
rs46825835 289 N>H No Ensembl
rs264880737 410 R>W No Ensembl
rs13465575 546 W>R No Ensembl
rs1131753902 557 A>V No Ensembl

No associated diseases with Q9Z2A0

8 regional properties for Q9Z2A0

Type Name Position InterPro Accession
domain C2 domain 1 - 98 IPR000008-1
domain C2 domain 668 - 794 IPR000008-2
domain C2 domain 1535 - 1664 IPR000008-3
domain Protein kinase C-like, phorbol ester/diacylglycerol-binding domain 562 - 612 IPR002219
domain MUN domain 1002 - 1521 IPR010439
domain Munc13 homology 1 1102 - 1245 IPR014770
domain Mammalian uncoordinated homology 13, domain 2 1354 - 1521 IPR014772
domain Protein Unc-13, C2B domain 685 - 811 IPR037302

Functions

Description
EC Number 2.7.11.1 Protein-serine/threonine kinases
Subcellular Localization
  • Cytoplasm
  • Nucleus
  • Cell membrane ; Peripheral membrane protein
  • Cell junction, focal adhesion
  • 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)
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

9 GO annotations of cellular component

Name Definition
cell projection A prolongation or process extending from a cell, e.g. a flagellum or axon.
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
cytoplasmic vesicle A vesicle found in the cytoplasm of a cell.
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
focal adhesion A cell-substrate junction that anchors the cell to the extracellular matrix and that forms a point of termination of actin filaments. In insects focal adhesion has also been referred to as hemi-adherens junction (HAJ).
nucleus A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.
perikaryon The portion of the cell soma (neuronal cell body) that excludes the nucleus.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
postsynaptic density An electron dense network of proteins within and adjacent to the postsynaptic membrane of an asymmetric, neuron-neuron synapse. Its major components include neurotransmitter receptors and the proteins that spatially and functionally organize them such as anchoring and scaffolding molecules, signaling enzymes and cytoskeletal components.

9 GO annotations of molecular function

Name Definition
3-phosphoinositide-dependent protein kinase activity Phosphatidylinositol-3-phosphate-dependent catalysis of the reaction: ATP + a protein = ADP + a phosphoprotein.
ATP binding Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
insulin receptor binding Binding to an insulin receptor.
phospholipase activator activity Increases the activity of a phospholipase, an enzyme that catalyzes of the hydrolysis of a glycerophospholipid.
phospholipase binding Binding to a phospholipase.
protein kinase binding Binding to a protein kinase, any enzyme that catalyzes the transfer of a phosphate group, usually from ATP, to a protein substrate.
protein serine kinase activity Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate.
protein serine/threonine kinase activity Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate, and ATP + protein threonine = ADP + protein threonine phosphate.
protein serine/threonine/tyrosine kinase activity Catalysis of the reactions: ATP + a protein serine = ADP + protein serine phosphate; ATP + a protein threonine = ADP + protein threonine phosphate; and ATP + a protein tyrosine = ADP + protein tyrosine phosphate.

29 GO annotations of biological process

Name Definition
activation of protein kinase B activity Any process that initiates the activity of the inactive enzyme protein kinase B.
calcium-mediated signaling Any intracellular signal transduction in which the signal is passed on within the cell via calcium ions.
cell migration The controlled self-propelled movement of a cell from one site to a destination guided by molecular cues. Cell migration is a central process in the development and maintenance of multicellular organisms.
cellular response to epidermal growth factor stimulus Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an epidermal growth factor stimulus.
cellular response to insulin stimulus Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an insulin stimulus. Insulin is a polypeptide hormone produced by the islets of Langerhans of the pancreas in mammals, and by the homologous organs of other organisms.
epidermal growth factor receptor signaling pathway The series of molecular signals initiated by binding of a ligand to the tyrosine kinase receptor EGFR (ERBB1) on the surface of a cell. The pathway ends with regulation of a downstream cellular process, e.g. transcription.
extrinsic apoptotic signaling pathway The series of molecular signals in which a signal is conveyed from the cell surface to trigger the apoptotic death of a cell. The pathway starts with either a ligand binding to a cell surface receptor, or a ligand being withdrawn from a cell surface receptor (e.g. in the case of signaling by dependence receptors), and ends when the execution phase of apoptosis is triggered.
focal adhesion assembly The aggregation and bonding together of a set of components to form a focal adhesion, a complex of intracellular signaling and structural proteins that provides a structural link between the internal actin cytoskeleton and the ECM, and also function as a locus of signal transduction activity.
hyperosmotic response Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of detection of, or exposure to, a hyperosmotic environment, i.e. an environment with a higher concentration of solutes than the organism or cell.
intracellular signal transduction The process in which a signal is passed on to downstream components within the cell, which become activated themselves to further propagate the signal and finally trigger a change in the function or state of the cell.
negative regulation of cardiac muscle cell apoptotic process Any process that decreases the rate or extent of cardiac cell apoptotic process, a form of programmed cell death induced by external or internal signals that trigger the activity of proteolytic caspases whose actions dismantle a cardiac muscle cell and result in its death.
negative regulation of endothelial cell apoptotic process Any process that stops, prevents or reduces the frequency, rate or extent of endothelial cell apoptotic process.
negative regulation of neuron apoptotic process Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process in neurons.
negative regulation of protein kinase activity Any process that stops, prevents, or reduces the frequency, rate or extent of protein kinase activity.
negative regulation of toll-like receptor signaling pathway Any process that stops, prevents, or reduces the frequency, rate, or extent of toll-like receptor signaling pathway.
negative regulation of transforming growth factor beta receptor signaling pathway Any process that stops, prevents, or reduces the frequency, rate or extent of any TGF-beta receptor signaling pathway.
peptidyl-serine phosphorylation The phosphorylation of peptidyl-serine to form peptidyl-O-phospho-L-serine.
peptidyl-threonine phosphorylation The phosphorylation of peptidyl-threonine to form peptidyl-O-phospho-L-threonine.
positive regulation of blood vessel endothelial cell migration Any process that activates or increases the frequency, rate or extent of the migration of the endothelial cells of blood vessels.
positive regulation of phospholipase activity Any process that increases the frequency, rate or extent of phospholipase activity, the hydrolysis of a phospholipid.
positive regulation of protein localization to plasma membrane Any process that activates or increases the frequency, rate or extent of protein localization to plasma membrane.
positive regulation of release of sequestered calcium ion into cytosol Any process that activates or increases the frequency, rate or extent of the release into the cytosolic compartment of calcium ions sequestered in the endoplasmic reticulum or mitochondria.
positive regulation of sprouting angiogenesis Any process that activates or increases the frequency, rate or extent of sprouting angiogenesis.
positive regulation of vascular endothelial cell proliferation Any process that activates or increases the frequency, rate or extent of vascular endothelial cell proliferation.
regulation of endothelial cell migration Any process that modulates the rate, frequency, or extent of the orderly movement of an endothelial cell into the extracellular matrix to form an endothelium.
regulation of I-kappaB kinase/NF-kappaB signaling Any process that modulates I-kappaB kinase/NF-kappaB signaling.
regulation of mast cell degranulation Any process that modulates the frequency, rate, or extent of mast cell degranulation.
signal transduction The cellular process in which a signal is conveyed to trigger a change in the activity or state of a cell. Signal transduction begins with reception of a signal (e.g. a ligand binding to a receptor or receptor activation by a stimulus such as light), or for signal transduction in the absence of ligand, signal-withdrawal or the activity of a constitutively active receptor. Signal transduction ends with regulation of a downstream cellular process, e.g. regulation of transcription or regulation of a metabolic process. Signal transduction covers signaling from receptors located on the surface of the cell and signaling via molecules located within the cell. For signaling between cells, signal transduction is restricted to events at and within the receiving cell.
type B pancreatic cell development The process whose specific outcome is the progression of a type B pancreatic cell over time, from its formation to the mature structure. A type B pancreatic cell is a cell located towards center of the islets of Langerhans that secretes insulin.

26 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q03407 PKH1 Serine/threonine-protein kinase PKH1 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) PR
Q9W0V1 Pdk1 3-phosphoinositide-dependent protein kinase 1 Drosophila melanogaster (Fruit fly) SS
O15530 PDPK1 3-phosphoinositide-dependent protein kinase 1 Homo sapiens (Human) EV
Q6A1A2 PDPK2P Putative 3-phosphoinositide-dependent protein kinase 2 Homo sapiens (Human) PR
Q02956 Prkcz Protein kinase C zeta type Mus musculus (Mouse) SS
Q62074 Prkci Protein kinase C iota type Mus musculus (Mouse) SS
P70268 Pkn1 Serine/threonine-protein kinase N1 Mus musculus (Mouse) SS
Q8K045 Pkn3 Serine/threonine-protein kinase N3 Mus musculus (Mouse) SS
Q8BWW9 Pkn2 Serine/threonine-protein kinase N2 Mus musculus (Mouse) SS
P23298 Prkch Protein kinase C eta type Mus musculus (Mouse) PR
P16054 Prkce Protein kinase C epsilon type Mus musculus (Mouse) PR
Q02111 Prkcq Protein kinase C theta type Mus musculus (Mouse) PR
P28867 Prkcd Protein kinase C delta type Mus musculus (Mouse) PR
P20444 Prkca Protein kinase C alpha type Mus musculus (Mouse) SS
P63318 Prkcg Protein kinase C gamma type Mus musculus (Mouse) SS
P68404 Prkcb Protein kinase C beta type Mus musculus (Mouse) SS
Q60823 Akt2 RAC-beta serine/threonine-protein kinase Mus musculus (Mouse) PR
P31750 Akt1 RAC-alpha serine/threonine-protein kinase Mus musculus (Mouse) PR
Q9WUA6 Akt3 RAC-gamma serine/threonine-protein kinase Mus musculus (Mouse) PR
Q9ERE3 Sgk3 Serine/threonine-protein kinase Sgk3 Mus musculus (Mouse) PR
Q8QZV4 Stk32c Serine/threonine-protein kinase 32C Mus musculus (Mouse) PR
Q91VJ4 Stk38 Serine/threonine-protein kinase 38 Mus musculus (Mouse) SS
Q7TSE6 Stk38l Serine/threonine-protein kinase 38-like Mus musculus (Mouse) SS
O55173 Pdpk1 3-phosphoinositide-dependent protein kinase 1 Rattus norvegicus (Rat) SS
Q9Y1J3 pdk-1 3-phosphoinositide-dependent protein kinase 1 Caenorhabditis elegans SS
Q4V3C8 PDPK2 3-phosphoinositide-dependent protein kinase 2 Arabidopsis thaliana (Mouse-ear cress) PR
10 20 30 40 50 60
MARTTSQLYD AVPIQSSVVL CSCPSPSMVR SQTEPGSSPG IPSGVSRQGS TMDGTTAEAR
70 80 90 100 110 120
PSTNPLQQHP AQLPPQPRKK RPEDFKFGKI LGEGSFSTVV LARELATSRE YAIKILEKRH
130 140 150 160 170 180
IIKENKVPYV TRERDVMSRL DHPFFVKLYF TFQDDEKLYF GLSYAKNGEL LKYIRKIGSF
190 200 210 220 230 240
DETCTRFYTA EIVSALEYLH GKGIIHRDLK PENILLNEDM HIQITDFGTA KVLSPESKQA
250 260 270 280 290 300
RANSFVGTAQ YVSPELLTEK SACKSSDLWA LGCIIYQLVA GLPPFRAGNE YLIFQKIIKL
310 320 330 340 350 360
EYHFPEKFFP KARDLVEKLL VLDATKRLGC EEMEGYGPLK AHPFFETITW ENLHQQTPPK
370 380 390 400 410 420
LTAYLPAMSE DDEDCYGNYD NLLSQFGFMQ VSSSSSSHSL STVETSLPQR SGSNIEQYIH
430 440 450 460 470 480
DLDTNSFELD LQFSEDEKRL LLEKQAGGNP WHQFVENNLI LKMGPVDKRK GLFARRRQLL
490 500 510 520 530 540
LTEGPHLYYV DPVNKVLKGE IPWSQELRPE AKNFKTFFVH TPNRTYYLMD PSGNAHKWCR
550
KIQEVWRQQY QSNPDAAVQ