P09217
SS
Gene name |
Prkcz (Pkcz) |
Protein name |
Protein kinase C zeta type |
Names |
EC 2.7.11.13 , nPKC-zeta |
Species |
Rattus norvegicus (Rat) |
KEGG Pathway |
rno:25522 |
EC number |
2.7.11.13: Protein-serine/threonine kinases |
Protein Class |
|
Descriptions
PRKCI, an atypical PKC (aPKC) isoform, is an important kinase in multiple cellular processes and regulated by the phosphatidylinositol 3-kinase product phosphatidylinositol 3,4,5-(PO4)3 (PIP3). In aPKC molecule, the arginine motif (123-140) in the pseudosubstrate region on the regulatory domain binds to acidic residues in the substrate-binding region on the catalytic domain, leading to the off state of aPKCs. The autoinhibition of aPKC is released by binding with the acidic ligand PIP3 and consequently exposing the substrate-binding site.
Autoinhibitory domains (AIDs)
Target domain |
227-592 (Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C iota) |
Relief mechanism |
Ligand binding |
Assay |
|
Accessory elements
No accessory elements
References
- Ivey RA et al. (2014) "Requirements for pseudosubstrate arginine residues during autoinhibition and phosphatidylinositol 3,4,5-(PO₄)₃-dependent activation of atypical PKC", The Journal of biological chemistry, 289, 25021-30
- Huang X et al. (2003) "Crystal structure of an inactive Akt2 kinase domain", Structure (London, England : 1993), 11, 21-30
- Truebestein L et al. (2021) "Structure of autoinhibited Akt1 reveals mechanism of PIP(3)-mediated activation", Proceedings of the National Academy of Sciences of the United States of America, 118,
- Lučić I et al. (2018) "Conformational sampling of membranes by Akt controls its activation and inactivation", Proceedings of the National Academy of Sciences of the United States of America, 115, E3940-E3949
Autoinhibited structure
Activated structure
2 structures for P09217
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| 4MJS | X-ray | 250 A | A/C/E/G/I/K/M/O/Q/S/U/W | 15-101 | PDB |
| AF-P09217-F1 | Predicted | AlphaFoldDB |
4 variants for P09217
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs198505812 | 75 | E>D | No | EVA | |
| rs197036704 | 178 | L>M | No | EVA | |
| rs105644854 | 181 | R>S | No | EVA | |
| rs198548520 | 505 | P>L | No | EVA |
No associated diseases with P09217
14 regional properties for P09217
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | PB1 domain | 15 - 98 | IPR000270 |
| domain | Protein kinase domain | 252 - 518 | IPR000719 |
| domain | AGC-kinase, C-terminal | 519 - 590 | IPR000961 |
| domain | Protein kinase C-like, phorbol ester/diacylglycerol-binding domain | 130 - 182 | IPR002219 |
| active_site | Serine/threonine-protein kinase, active site | 372 - 384 | IPR008271 |
| binding_site | Protein kinase, ATP binding site | 258 - 285 | IPR017441 |
| domain | Protein kinase, C-terminal | 540 - 580 | IPR017892 |
| domain | Diacylglycerol/phorbol-ester binding | 128 - 142 | IPR020454-1 |
| domain | Diacylglycerol/phorbol-ester binding | 144 - 153 | IPR020454-2 |
| domain | Diacylglycerol/phorbol-ester binding | 157 - 168 | IPR020454-3 |
| domain | Diacylglycerol/phorbol-ester binding | 169 - 181 | IPR020454-4 |
| domain | Protein kinase C, PB1 domain | 16 - 98 | IPR034877 |
| domain | Protein kinase C zeta type, conserved region 1 | 129 - 183 | IPR047314 |
| domain | PB1-like domain | 15 - 98 | IPR053793 |
Functions
| Description | ||
|---|---|---|
| EC Number | 2.7.11.13 | Protein-serine/threonine kinases |
| Subcellular Localization |
|
|
| PANTHER Family | ||
| PANTHER Subfamily | ||
| PANTHER Protein Class | ||
| PANTHER Pathway Category | No pathway information available | |
22 GO annotations of cellular component
| Name | Definition |
|---|---|
| apical cortex | The region that lies just beneath the plasma membrane on the apical edge of a cell. |
| apical plasma membrane | The region of the plasma membrane located at the apical end of the cell. |
| axon hillock | Portion of the neuronal cell soma from which the axon originates. |
| bicellular tight junction | An occluding cell-cell junction that is composed of a branching network of sealing strands that completely encircles the apical end of each cell in an epithelial sheet; the outer leaflets of the two interacting plasma membranes are seen to be tightly apposed where sealing strands are present. Each sealing strand is composed of a long row of transmembrane adhesion proteins embedded in each of the two interacting plasma membranes. |
| cell cortex | The region of a cell that lies just beneath the plasma membrane and often, but not always, contains a network of actin filaments and associated proteins. |
| cell leading edge | The area of a motile cell closest to the direction of movement. |
| cell-cell junction | A cell junction that forms a connection between two or more cells of an organism; excludes direct cytoplasmic intercellular bridges, such as ring canals in insects. |
| cytoplasm | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. |
| cytosol | The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. |
| endosome | A vacuole to which materials ingested by endocytosis are delivered. |
| glutamatergic synapse | A synapse that uses glutamate as a neurotransmitter. |
| microtubule organizing center | An intracellular structure that can catalyze gamma-tubulin-dependent microtubule nucleation and that can anchor microtubules by interacting with their minus ends, plus ends or sides. |
| myelin sheath abaxonal region | The region of the myelin sheath furthest from the axon. |
| nuclear envelope | The double lipid bilayer enclosing the nucleus and separating its contents from the rest of the cytoplasm; includes the intermembrane space, a gap of width 20-40 nm (also called the perinuclear space). |
| nuclear matrix | The dense fibrillar network lying on the inner side of the nuclear membrane. |
| 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. |
| perinuclear region of cytoplasm | Cytoplasm situated near, or occurring around, 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. |
| Schaffer collateral - CA1 synapse | A synapse between the Schaffer collateral axon of a CA3 pyramidal cell and a CA1 pyramidal cell. |
| stress fiber | A contractile actin filament bundle that consists of short actin filaments with alternating polarity, cross-linked by alpha-actinin and possibly other actin bundling proteins, and with myosin present in a periodic distribution along the fiber. |
| vesicle | Any small, fluid-filled, spherical organelle enclosed by membrane. |
11 GO annotations of molecular function
| Name | Definition |
|---|---|
| 14-3-3 protein binding | Binding to a 14-3-3 protein. A 14-3-3 protein is any of a large family of approximately 30kDa acidic proteins which exist primarily as homo- and heterodimers within all eukaryotic cells, and have been implicated in the modulation of distinct biological processes by binding to specific phosphorylated sites on diverse target proteins, thereby forcing conformational changes or influencing interactions between their targets and other molecules. Each 14-3-3 protein sequence can be roughly divided into three sections |
| ATP binding | Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator. |
| diacylglycerol-dependent serine/threonine kinase activity | Catalysis of the reaction |
| metal ion binding | Binding to a metal ion. |
| phospholipase binding | Binding to a phospholipase. |
| potassium channel regulator activity | Binds to and modulates the activity of a potassium channel. |
| protein kinase activity | Catalysis of the phosphorylation of an amino acid residue in a protein, usually according to the reaction |
| 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 |
| protein serine/threonine kinase activity | Catalysis of the reactions |
| protein-containing complex binding | Binding to a macromolecular complex. |
35 GO annotations of biological process
| Name | Definition |
|---|---|
| cell migration | The controlled self-propelled movement of a cell from one site to a destination guided by molecular cues. |
| cell surface receptor signaling pathway | The series of molecular signals initiated by activation of a receptor on the surface of a cell. The pathway begins with binding of an extracellular ligand to a cell surface receptor, or for receptors that signal in the absence of a ligand, by ligand-withdrawal or the activity of a constitutively active receptor. The pathway ends with regulation of a downstream cellular process, e.g. transcription. |
| 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. |
| establishment of cell polarity | The specification and formation of anisotropic intracellular organization or cell growth patterns. |
| inflammatory response | The immediate defensive reaction (by vertebrate tissue) to infection or injury caused by chemical or physical agents. The process is characterized by local vasodilation, extravasation of plasma into intercellular spaces and accumulation of white blood cells and macrophages. |
| 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. |
| long-term memory | The memory process that deals with the storage, retrieval and modification of information a long time (typically weeks, months or years) after receiving that information. This type of memory is typically dependent on gene transcription regulated by second messenger activation. |
| long-term synaptic potentiation | A process that modulates synaptic plasticity such that synapses are changed resulting in the increase in the rate, or frequency of synaptic transmission at the synapse. |
| membrane depolarization | The process in which membrane potential decreases with respect to its steady-state potential, usually from negative potential to a more positive potential. For example, the initial depolarization during the rising phase of an action potential is in the direction from the negative steady-state resting potential towards the positive membrane potential that will be the peak of the action potential. |
| membrane hyperpolarization | The process in which membrane potential increases with respect to its steady-state potential, usually from negative potential to a more negative potential. For example, during the repolarization phase of an action potential the membrane potential often becomes more negative or hyperpolarized before returning to the steady-state resting potential. |
| microtubule cytoskeleton organization | A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of cytoskeletal structures comprising microtubules and their associated proteins. |
| negative regulation of apoptotic process | Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process. |
| negative regulation of insulin receptor signaling pathway | Any process that stops, prevents, or reduces the frequency, rate or extent of insulin receptor signaling. |
| negative regulation of peptidyl-tyrosine phosphorylation | Any process that stops, prevents, or reduces the frequency, rate or extent of the phosphorylation of peptidyl-tyrosine. |
| negative regulation of protein-containing complex assembly | Any process that stops, prevents, or reduces the frequency, rate or extent of protein complex assembly. |
| neuron projection extension | Long distance growth of a single neuron projection involved in cellular development. A neuron projection is a prolongation or process extending from a nerve cell, e.g. an axon or dendrite. |
| phosphorylation | The process of introducing a phosphate group into a molecule, usually with the formation of a phosphoric ester, a phosphoric anhydride or a phosphoric amide. |
| positive regulation of cell population proliferation | Any process that activates or increases the rate or extent of cell proliferation. |
| positive regulation of cell-matrix adhesion | Any process that activates or increases the rate or extent of cell adhesion to an extracellular matrix. |
| positive regulation of ERK1 and ERK2 cascade | Any process that activates or increases the frequency, rate or extent of signal transduction mediated by the ERK1 and ERK2 cascade. |
| positive regulation of excitatory postsynaptic potential | Any process that enhances the establishment or increases the extent of the excitatory postsynaptic potential (EPSP) which is a temporary increase in postsynaptic potential due to the flow of positively charged ions into the postsynaptic cell. The flow of ions that causes an EPSP is an excitatory postsynaptic current (EPSC) and makes it easier for the neuron to fire an action potential. |
| positive regulation of insulin receptor signaling pathway | Any process that increases the frequency, rate or extent of insulin receptor signaling. |
| positive regulation of interleukin-10 production | Any process that activates or increases the frequency, rate, or extent of interleukin-10 production. |
| positive regulation of interleukin-13 production | Any process that activates or increases the frequency, rate, or extent of interleukin-13 production. |
| positive regulation of interleukin-4 production | Any process that activates or increases the frequency, rate, or extent of interleukin-4 production. |
| positive regulation of interleukin-5 production | Any process that activates or increases the frequency, rate, or extent of interleukin-5 production. |
| positive regulation of NF-kappaB transcription factor activity | Any process that activates or increases the frequency, rate or extent of activity of the transcription factor NF-kappaB. |
| positive regulation of protein transport | Any process that activates or increases the frequency, rate or extent of the directed movement of a protein into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. |
| positive regulation of synaptic transmission | Any process that activates or increases the frequency, rate or extent of synaptic transmission, the process of communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. |
| positive regulation of T-helper 2 cell cytokine production | Any process that activates or increases the frequency, rate or extent of T-helper 2 cell cytokine production. |
| positive regulation of T-helper 2 cell differentiation | Any process that activates or increases the frequency, rate or extent of T-helper 2 cell differentiation. |
| protein kinase C signaling | A series of reactions, mediated by the intracellular serine/threonine kinase protein kinase C, which occurs as a result of a single trigger reaction or compound. |
| protein localization to plasma membrane | A process in which a protein is transported to, or maintained in, a specific location in the plasma membrane. |
| regulation of neurotransmitter receptor localization to postsynaptic specialization membrane | Any process that modulates the frequency, rate or extent of neurotransmitter receptor localization to postsynaptic specialization membrane. |
| vesicle transport along microtubule | The directed movement of a vesicle along a microtubule, mediated by motor proteins. This process begins with the attachment of a vesicle to a microtubule, and ends when the vesicle reaches its final destination. |
21 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| P24583 | PKC1 | Protein kinase C-like 1 | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) | SS |
| A1Z9X0 | aPKC | Atypical protein kinase C | Drosophila melanogaster (Fruit fly) | SS |
| P41743 | PRKCI | Protein kinase C iota type | Homo sapiens (Human) | EV |
| Q05513 | PRKCZ | Protein kinase C zeta type | Homo sapiens (Human) | SS |
| Q62074 | Prkci | Protein kinase C iota type | Mus musculus (Mouse) | SS |
| Q02956 | Prkcz | Protein kinase C zeta type | Mus musculus (Mouse) | SS |
| O55173 | Pdpk1 | 3-phosphoinositide-dependent protein kinase 1 | Rattus norvegicus (Rat) | SS |
| F1M7Y5 | Prkci | Protein kinase C iota type | Rattus norvegicus (Rat) | SS |
| Q63433 | Pkn1 | Serine/threonine-protein kinase N1 | Rattus norvegicus (Rat) | SS |
| Q64617 | Prkch | Protein kinase C eta type | Rattus norvegicus (Rat) | PR |
| P09215 | Prkcd | Protein kinase C delta type | Rattus norvegicus (Rat) | PR |
| P63319 | Prkcg | Protein kinase C gamma type | Rattus norvegicus (Rat) | SS |
| P47197 | Akt2 | RAC-beta serine/threonine-protein kinase | Rattus norvegicus (Rat) | SS |
| P47196 | Akt1 | RAC-alpha serine/threonine-protein kinase | Rattus norvegicus (Rat) | PR |
| Q63484 | Akt3 | RAC-gamma serine/threonine-protein kinase | Rattus norvegicus (Rat) | PR |
| O08874 | Pkn2 | Serine/threonine-protein kinase N2 | Rattus norvegicus (Rat) | SS |
| P09216 | Prkce | Protein kinase C epsilon type | Rattus norvegicus (Rat) | PR |
| P05696 | Prkca | Protein kinase C alpha type | Rattus norvegicus (Rat) | SS |
| P68403 | Prkcb | Protein kinase C beta type | Rattus norvegicus (Rat) | SS |
| Q19266 | pkc-3 | Protein kinase C-like 3 | Caenorhabditis elegans | SS |
| Q90XF2 | prkci | Protein kinase C iota type | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MPSRTDPKMD | RSGGRVRLKA | HYGGDILITS | VDPTTTFQDL | CEEVRDMCGL | HQQHPLTLKW |
| 70 | 80 | 90 | 100 | 110 | 120 |
| VDSEGDPCTV | SSQMELEEAF | RLACQGRDEV | LIIHVFPSIP | EQPGMPCPGE | DKSIYRRGAR |
| 130 | 140 | 150 | 160 | 170 | 180 |
| RWRKLYRANG | HLFQAKRFNR | RAYCGQCSER | IWGLARQGYR | CINCKLLVHK | RCHVLVPLTC |
| 190 | 200 | 210 | 220 | 230 | 240 |
| RRHMDSVMPS | QEPPVDDKND | GVDLPSEETD | GIAYISSSRK | HDNIKDDSED | LKPVIDGVDG |
| 250 | 260 | 270 | 280 | 290 | 300 |
| IKISQGLGLQ | DFDLIRVIGR | GSYAKVLLVR | LKKNDQIYAM | KVVKKELVHD | DEDIDWVQTE |
| 310 | 320 | 330 | 340 | 350 | 360 |
| KHVFEQASSN | PFLVGLHSCF | QTTSRLFLVI | EYVNGGDLMF | HMQRQRKLPE | EHARFYAAEI |
| 370 | 380 | 390 | 400 | 410 | 420 |
| CIALNFLHER | GIIYRDLKLD | NVLLDADGHI | KLTDYGMCKE | GLGPGDTTST | FCGTPNYIAP |
| 430 | 440 | 450 | 460 | 470 | 480 |
| EILRGEEYGF | SVDWWALGVL | MFEMMAGRSP | FDIITDNPDM | NTEDYLFQVI | LEKPIRIPRF |
| 490 | 500 | 510 | 520 | 530 | 540 |
| LSVKASHVLK | GFLNKDPKER | LGCRPQTGFS | DIKSHAFFRS | IDWDLLEKKQ | TLPPFQPQIT |
| 550 | 560 | 570 | 580 | 590 | |
| DDYGLDNFDT | QFTSEPVQLT | PDDEDVIKRI | DQSEFEGFEY | INPLLLSAEE | SV |