P63318
Gene name |
Prkcg (Pkcc, Pkcg, Prkcc) |
Protein name |
Protein kinase C gamma type |
Names |
PKC-gamma , EC 2.7.11.13 |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:18752 |
EC number |
2.7.11.13: Protein-serine/threonine kinases |
Protein Class |
|
Descriptions
Autoinhibitory domains (AIDs)
Target domain |
340-685 (Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C alpha) |
Relief mechanism |
Ligand binding |
Assay |
|
Target domain |
340-685 (Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C alpha) |
Relief mechanism |
Ligand binding |
Assay |
|
Target domain |
353-600 (Protein kinase domain) |
Relief mechanism |
Ligand binding |
Assay |
|
Target domain |
353-600 (Protein kinase domain) |
Relief mechanism |
Ligand binding |
Assay |
|
Accessory elements
497-520 (Activation loop from InterPro)
Target domain |
351-614 (Protein kinase domain) |
Relief mechanism |
|
Assay |
|
References
- Steinberg SF (2008) "Structural basis of protein kinase C isoform function", Physiological reviews, 88, 1341-78
- Sommese RF et al. (2017) "The Role of Regulatory Domains in Maintaining Autoinhibition in the Multidomain Kinase PKCα", The Journal of biological chemistry, 292, 2873-2880
- Pears CJ et al. (1990) "Mutagenesis of the pseudosubstrate site of protein kinase C leads to activation", European journal of biochemistry, 194, 89-94
- Smith MK et al. (1990) "Specificities of autoinhibitory domain peptides for four protein kinases. Implications for intact cell studies of protein kinase function", The Journal of biological chemistry, 265, 1837-40
- Slater SJ et al. (2002) "Regulation of PKC alpha activity by C1-C2 domain interactions", The Journal of biological chemistry, 277, 15277-85
- Jones AC et al. (2020) "Hypothesis: Unifying model of domain architecture for conventional and novel protein kinase C isozymes", IUBMB life, 72, 2584-2590
- Kirwan AF et al. (2003) "Inhibition of protein kinase C catalytic activity by additional regions within the human protein kinase Calpha-regulatory domain lying outside of the pseudosubstrate sequence", The Biochemical journal, 373, 571-81
- 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
- Wagner J et al. (2009) "Discovery of 3-(1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione (AEB071), a potent and selective inhibitor of protein kinase C isotypes", Journal of medicinal chemistry, 52, 6193-6
- Yeon JH et al. (2016) "Systems-wide Identification of cis-Regulatory Elements in Proteins", Cell systems, 2, 89-100
Autoinhibited structure
Activated structure
1 structures for P63318
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-P63318-F1 | Predicted | AlphaFoldDB |
28 variants for P63318
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs3388865367 | 19 | F>L | No | EVA | |
| rs3388870748 | 52 | C>* | No | EVA | |
| rs3388870774 | 53 | T>S | No | EVA | |
| rs3388870791 | 110 | S>N | No | EVA | |
| rs3388869562 | 148 | S>P | No | EVA | |
| rs3388873997 | 203 | D>H | No | EVA | |
| rs3388870958 | 207 | L>P | No | EVA | |
| rs3388873403 | 210 | Q>H | No | EVA | |
| rs3388865350 | 218 | T>S | No | EVA | |
| rs3388847004 | 241 | S>R | No | EVA | |
| rs3388834741 | 288 | V>L | No | EVA | |
| rs3388870718 | 290 | V>M | No | EVA | |
| rs3388873917 | 325 | P>H | No | EVA | |
| rs3388862172 | 375 | E>V | No | EVA | |
| rs3388873322 | 387 | I>V | No | EVA | |
| rs3397565333 | 406 | G>A | No | EVA | |
| rs3388862181 | 411 | G>R | No | EVA | |
| rs3388846932 | 416 | F>S | No | EVA | |
| rs3388875245 | 417 | L>F | No | EVA | |
| rs3412949284 | 446 | I>V | No | EVA | |
| rs3388878024 | 456 | H>Y | No | EVA | |
| rs3388870986 | 518 | T>I | No | EVA | |
| rs3396798218 | 546 | Y>* | No | EVA | |
| rs3388873443 | 613 | F>L | No | EVA | |
| rs3388853518 | 623 | E>G | No | EVA | |
| rs3388865731 | 642 | N>K | No | EVA | |
| rs3388865670 | 657 | P>Q | No | EVA | |
| rs3388865323 | 660 | L>F | No | EVA |
No associated diseases with P63318
8 regional properties for P63318
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| binding_site | IQ motif, EF-hand binding site | 689 - 711 | IPR000048-1 |
| binding_site | IQ motif, EF-hand binding site | 719 - 741 | IPR000048-2 |
| binding_site | IQ motif, EF-hand binding site | 749 - 771 | IPR000048-3 |
| domain | RasGAP protein, C-terminal | 1367 - 1498 | IPR000593 |
| domain | WW domain | 594 - 627 | IPR001202 |
| domain | Calponin homology domain | 41 - 156 | IPR001715 |
| domain | Ras GTPase-activating domain | 905 - 1258 | IPR001936 |
| conserved_site | Ras GTPase-activating protein, conserved site | 1102 - 1116 | IPR023152 |
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 | |
12 GO annotations of cellular component
| Name | Definition |
|---|---|
| calyx of Held | The terminal specialization of a calyciferous axon which forms large synapses in the mammalian auditory central nervous system. |
| 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. |
| dendrite | A neuron projection that has a short, tapering, morphology. Dendrites receive and integrate signals from other neurons or from sensory stimuli, and conduct nerve impulses towards the axon or the cell body. In most neurons, the impulse is conveyed from dendrites to axon via the cell body, but in some types of unipolar neuron, the impulse does not travel via the cell body. |
| 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 cytosol | The region of the cytosol consisting of all cytosol that is part of the postsynapse. |
| 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. |
| presynaptic cytosol | The region of the cytosol consisting of all cytosol that is part of the presynapse. |
| synaptic membrane | A specialized area of membrane on either the presynaptic or the postsynaptic side of a synapse, the junction between a nerve fiber of one neuron and another neuron or muscle fiber or glial cell. |
7 GO annotations of molecular function
| Name | Definition |
|---|---|
| ATP binding | Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator. |
| calcium,diacylglycerol-dependent serine/threonine kinase activity | Calcium-dependent catalysis of the reaction |
| diacylglycerol-dependent serine/threonine kinase activity | Catalysis of the reaction |
| protein serine kinase activity | Catalysis of the reactions |
| protein serine/threonine kinase activity | Catalysis of the reactions |
| protein serine/threonine/tyrosine kinase activity | Catalysis of the reactions |
| zinc ion binding | Binding to a zinc ion (Zn). |
21 GO annotations of biological process
| Name | Definition |
|---|---|
| chemical synaptic transmission | The vesicular release of classical neurotransmitter molecules from a presynapse, across a chemical synapse, the subsequent activation of neurotransmitter receptors at the postsynapse of a target cell (neuron, muscle, or secretory cell) and the effects of this activation on the postsynaptic membrane potential and ionic composition of the postsynaptic cytosol. This process encompasses both spontaneous and evoked release of neurotransmitter and all parts of synaptic vesicle exocytosis. Evoked transmission starts with the arrival of an action potential at the presynapse. |
| chemosensory behavior | Behavior that is dependent upon the sensation of chemicals. |
| innervation | The process in which a nerve invades a tissue and makes functional synaptic connection within the tissue. |
| 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. |
| learning or memory | The acquisition and processing of information and/or the storage and retrieval of this information over time. |
| 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. |
| 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 proteasomal protein catabolic process | Any process that stops, prevents or reduces the frequency, rate or extent of proteasomal protein catabolic process. |
| negative regulation of protein ubiquitination | Any process that stops, prevents, or reduces the frequency, rate or extent of the addition of ubiquitin groups to a protein. |
| 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 mismatch repair | Any process that activates or increases the frequency, rate or extent of mismatch repair. |
| presynaptic modulation of chemical synaptic transmission | Any process, acting in the presynapse that results in modulation of chemical synaptic transmission. |
| regulation of circadian rhythm | Any process that modulates the frequency, rate or extent of a circadian rhythm. A circadian rhythm is a biological process in an organism that recurs with a regularity of approximately 24 hours. |
| regulation of phagocytosis | Any process that modulates the frequency, rate or extent of phagocytosis, the process in which phagocytes engulf external particulate material. |
| regulation of response to food | Any process that modulates the frequency, rate or extent of a response to a food stimulus. |
| regulation of synaptic vesicle exocytosis | Any process that modulates the frequency, rate or extent of synaptic vesicle exocytosis. |
| response to morphine | 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 a morphine stimulus. Morphine is an opioid alkaloid, isolated from opium, with a complex ring structure. |
| response to pain | 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 a pain stimulus. Pain stimuli cause activation of nociceptors, peripheral receptors for pain, include receptors which are sensitive to painful mechanical stimuli, extreme heat or cold, and chemical stimuli. |
| response to psychosocial stress | 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 exposure to aversive or demanding psychological and social conditions that tax or exceed the behavioral resources of the organism. |
| response to toxic substance | 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 a toxic stimulus. |
| rhythmic process | Any process pertinent to the generation and maintenance of rhythms in the physiology of an organism. |
37 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 |
| P04409 | PRKCA | Protein kinase C alpha type | Bos taurus (Bovine) | EV SS |
| P05126 | PRKCB | Protein kinase C beta type | Bos taurus (Bovine) | SS |
| P05128 | PRKCG | Protein kinase C gamma type | Bos taurus (Bovine) | SS |
| P13677 | inaC | Protein kinase C, eye isozyme | Drosophila melanogaster (Fruit fly) | SS |
| P05130 | Pkc53E | Protein kinase C, brain isozyme | Drosophila melanogaster (Fruit fly) | SS |
| P05771 | PRKCB | Protein kinase C beta type | Homo sapiens (Human) | SS |
| P17252 | PRKCA | Protein kinase C alpha type | Homo sapiens (Human) | EV |
| P05129 | PRKCG | Protein kinase C gamma type | Homo sapiens (Human) | SS |
| Q02156 | PRKCE | Protein kinase C epsilon type | Homo sapiens (Human) | SS |
| P24723 | PRKCH | Protein kinase C eta type | Homo sapiens (Human) | SS |
| Q9Z2A0 | Pdpk1 | 3-phosphoinositide-dependent protein kinase 1 | Mus musculus (Mouse) | SS |
| 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 |
| 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 |
| P05696 | Prkca | Protein kinase C alpha type | Rattus norvegicus (Rat) | SS |
| P68403 | Prkcb | Protein kinase C beta type | Rattus norvegicus (Rat) | SS |
| P63319 | Prkcg | Protein kinase C gamma type | Rattus norvegicus (Rat) | SS |
| Q64617 | Prkch | Protein kinase C eta type | Rattus norvegicus (Rat) | PR |
| P90980 | pkc-2 | Protein kinase C-like 2 | Caenorhabditis elegans | SS |
| A8KBH6 | prkcb | Protein kinase C beta type | Xenopus tropicalis (Western clawed frog) (Silurana tropicalis) | SS |
| Q7SY24 | prkcbb | Protein kinase C beta type | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MAGLGPGGGD | SEGGPRPLFC | RKGALRQKVV | HEVKSHKFTA | RFFKQPTFCS | HCTDFIWGIG |
| 70 | 80 | 90 | 100 | 110 | 120 |
| KQGLQCQVCS | FVVHRRCHEF | VTFECPGAGK | GPQTDDPRNK | HKFRLHSYSS | PTFCDHCGSL |
| 130 | 140 | 150 | 160 | 170 | 180 |
| LYGLVHQGMK | CSCCEMNVHR | RCVRSVPSLC | GVDHTERRGR | LQLEIRAPTS | DEIHITVGEA |
| 190 | 200 | 210 | 220 | 230 | 240 |
| RNLIPMDPNG | LSDPYVKLKL | IPDPRNLTKQ | KTKTVKATLN | PVWNETFVFN | LKPGDVERRL |
| 250 | 260 | 270 | 280 | 290 | 300 |
| SVEVWDWDRT | SRNDFMGAMS | FGVSELLKAP | VDGWYKLLNQ | EEGEYYNVPV | ADADNCSLLQ |
| 310 | 320 | 330 | 340 | 350 | 360 |
| KFEACNYPLE | LYERVRMGPS | SSPIPSPSPS | PTDSKRCFFG | ASPGRLHISD | FSFLMVLGKG |
| 370 | 380 | 390 | 400 | 410 | 420 |
| SFGKVMLAER | RGSDELYAIK | ILKKDVIVQD | DDVDCTLVEK | RVLALGGRGP | GGRPHFLTQL |
| 430 | 440 | 450 | 460 | 470 | 480 |
| HSTFQTPDRL | YFVMEYVTGG | DLMYHIQQLG | KFKEPHAAFY | AAEIAIGLFF | LHNQGIIYRD |
| 490 | 500 | 510 | 520 | 530 | 540 |
| LKLDNVMLDA | EGHIKITDFG | MCKENVFPGS | TTRTFCGTPD | YIAPEIIAYQ | PYGKSVDWWS |
| 550 | 560 | 570 | 580 | 590 | 600 |
| FGVLLYEMLA | GQPPFDGEDE | EELFQAIMEQ | TVTYPKSLSR | EAVAICKGFL | TKHPGKRLGS |
| 610 | 620 | 630 | 640 | 650 | 660 |
| GPDGEPTIRA | HGFFRWIDWE | RLERLEIAPP | FRPRPCGRSG | ENFDKFFTRA | APALTPPDRL |
| 670 | 680 | 690 | |||
| VLASIDQADF | QGFTYVNPDF | VHPDARSPTS | PVPVPVM |