P04409
Gene name |
PRKCA |
Protein name |
Protein kinase C alpha type |
Names |
PKC-A, PKC-alpha |
Species |
Bos taurus (Bovine) |
KEGG Pathway |
bta:282001 |
EC number |
2.7.11.13: Protein-serine/threonine kinases |
Protein Class |
RIBOSOMAL PROTEIN S6 KINASE (PTHR24351) |
Descriptions
Protein kinase C is a multi-module Ser/Thr protein kinase that transduces the abundance of signals resulting in phospholipid hydrolysis. Binding of diacylglycerol allosterically and reversibly activates these enzymes to affect their major role in maintaining cellular homeostasis. This allosteric regulation is precisely controlled by multiple mechanisms that ensure that the enzyme is only active for specific times at specific locations in response to specific signals.
PKC consists of a regulatory moiety (pseudosubstrate site, C1A and C1B able to bind phorbol esters and diacylglycerol, and calcium-binding C2 domain) and protein kinase domain. The kinase domain is followed by a C-Tail that is a hallmark regulatory region of AGC kinases and serves as a docking site for regulatory proteins.
The pseudosubstrate binds the substrate-binding cavity of the kinase domain and operates as an autoinhibitory segment. While the pseudosubstrate-C1A is the dominant autoinhibitory module and is necessary for the autoinhibition of all PKC family members, all domains in the regulatory module participate in a network of interactions to maintain autoinhibition.
Autoinhibitory domains (AIDs)
Target domain |
341-583 (Protein kinase domain) |
Relief mechanism |
|
Assay |
|
Target domain |
341-583 (Protein kinase domain) |
Relief mechanism |
Ligand binding |
Assay |
Mutagenesis experiment, Deletion assay |
Target domain |
341-583 (Protein kinase domain) |
Relief mechanism |
Ligand binding |
Assay |
Structural analysis, Mutagenesis experiment, Deletion assay |
Target domain |
341-583 (Protein kinase domain) |
Relief mechanism |
|
Assay |
Structural analysis, Mutagenesis experiment, Deletion assay |
Target domain |
341-583 (Protein kinase domain) |
Relief mechanism |
Ligand binding |
Assay |
Structural analysis, Mutagenesis experiment, Deletion assay |
Accessory elements
480-503 (Activation loop from InterPro)
Target domain |
328-668 (Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C alpha) |
Relief mechanism |
|
Assay |
|
References
- Yeon JH et al. (2016) "Systems-wide Identification of cis-Regulatory Elements in Proteins", Cell systems, 2, 89-100
- 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
- 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
Autoinhibited structure
Activated structure
1 structures for P04409
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-P04409-F1 | Predicted | AlphaFoldDB |
No variants for P04409
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| No variants for P04409 | |||||
No associated diseases with P04409
13 regional properties for P04409
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | C2 domain | 158 - 277 | IPR000008 |
| domain | Protein kinase domain | 339 - 597 | IPR000719 |
| domain | AGC-kinase, C-terminal | 598 - 668 | IPR000961 |
| domain | Protein kinase C-like, phorbol ester/diacylglycerol-binding domain | 36 - 87 | IPR002219-1 |
| domain | Protein kinase C-like, phorbol ester/diacylglycerol-binding domain | 101 - 153 | IPR002219-2 |
| active_site | Serine/threonine-protein kinase, active site | 459 - 471 | IPR008271 |
| binding_site | Protein kinase, ATP binding site | 345 - 368 | IPR017441 |
| domain | Protein kinase, C-terminal | 624 - 658 | IPR017892 |
| domain | Diacylglycerol/phorbol-ester binding | 34 - 48 | IPR020454-1 |
| domain | Diacylglycerol/phorbol-ester binding | 50 - 59 | IPR020454-2 |
| domain | Diacylglycerol/phorbol-ester binding | 63 - 74 | IPR020454-3 |
| domain | Diacylglycerol/phorbol-ester binding | 140 - 152 | IPR020454-4 |
| domain | Classical Protein Kinase C alpha, catalytic domain | 328 - 668 | IPR034663 |
Functions
| Description | ||
|---|---|---|
| EC Number | 2.7.11.13 | Protein-serine/threonine kinases |
| Subcellular Localization |
|
|
| PANTHER Family | PTHR24351 | RIBOSOMAL PROTEIN S6 KINASE |
| PANTHER Subfamily | PTHR24351:SF242 | PROTEIN KINASE C |
| PANTHER Protein Class | protein modifying enzyme | |
| PANTHER Pathway Category | No pathway information available | |
7 GO annotations of cellular component
| Name | Definition |
|---|---|
| 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. |
| mitochondrial membrane | Either of the lipid bilayers that surround the mitochondrion and form the mitochondrial envelope. |
| 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. |
| photoreceptor disc membrane | Stack of disc membranes located inside a photoreceptor outer segment, and containing densely packed molecules of photoreceptor proteins that traverse the lipid bilayer. Disc membranes arise as evaginations of the ciliary membrane during the development of the outer segment and may or may not remain contiguous with the ciliary membrane. |
| plasma membrane | The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins. |
8 GO annotations of molecular function
| Name | Definition |
|---|---|
| ATP binding | Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator. |
| calcium-dependent protein kinase C activity | Calcium-dependent catalysis of the reaction: ATP + a protein = ADP + a phosphoprotein. |
| PDZ domain binding | Binding to a PDZ domain of a protein, a domain found in diverse signaling proteins. |
| protein kinase C activity | Catalysis of the reaction: ATP + a protein = ADP + a phosphoprotein. This reaction requires diacylglycerol. |
| 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. |
| scaffold protein binding | Binding to a scaffold protein. Scaffold proteins are crucial regulators of many key signaling pathways. Although not strictly defined in function, they are known to interact and/or bind with multiple members of a signaling pathway, tethering them into complexes. |
| zinc ion binding | Binding to a zinc ion (Zn). |
20 GO annotations of biological process
| Name | Definition |
|---|---|
| angiogenesis | Blood vessel formation when new vessels emerge from the proliferation of pre-existing blood vessels. |
| apoptotic process | A programmed cell death process which begins when a cell receives an internal (e.g. DNA damage) or external signal (e.g. an extracellular death ligand), and proceeds through a series of biochemical events (signaling pathway phase) which trigger an execution phase. The execution phase is the last step of an apoptotic process, and is typically characterized by rounding-up of the cell, retraction of pseudopodes, reduction of cellular volume (pyknosis), chromatin condensation, nuclear fragmentation (karyorrhexis), plasma membrane blebbing and fragmentation of the cell into apoptotic bodies. When the execution phase is completed, the cell has died. |
| cell adhesion | The attachment of a cell, either to another cell or to an underlying substrate such as the extracellular matrix, via cell adhesion molecules. |
| 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 glial cell apoptotic process | Any process that stops, prevents, or reduces the frequency, rate, or extent of glial cell apoptotic process. |
| peptidyl-serine phosphorylation | The phosphorylation of peptidyl-serine to form peptidyl-O-phospho-L-serine. |
| positive regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway | Any process that activates or increases the frequency, rate or extent of an adenylate cyclase-activating G protein-coupled receptor signaling pathway. |
| positive regulation of angiogenesis | Any process that activates or increases angiogenesis. |
| positive regulation of cardiac muscle hypertrophy | Any process that increases the rate, frequency or extent of the enlargement or overgrowth of all or part of the heart due to an increase in size (not length) of individual cardiac muscle fibers, without cell division. |
| positive regulation of cell adhesion | Any process that activates or increases the frequency, rate or extent of cell adhesion. |
| positive regulation of cell migration | Any process that activates or increases the frequency, rate or extent of cell migration. |
| positive regulation of dense core granule biogenesis | Any process that activates or increases the frequency, rate or extent of dense core granule biogenesis. |
| positive regulation of endothelial cell migration | Any process that increases the rate, frequency, or extent of the orderly movement of an endothelial cell into the extracellular matrix to form an endothelium. |
| positive regulation of endothelial cell proliferation | Any process that activates or increases the rate or extent of endothelial cell proliferation. |
| 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 lipopolysaccharide-mediated signaling pathway | Any process that activates or increases the frequency, rate or extent of signaling in response to detection of lipopolysaccharide. |
| positive regulation of macrophage differentiation | Any process that activates or increases the frequency, rate or extent of macrophage differentiation. |
| positive regulation of mitotic cell cycle | Any process that activates or increases the rate or extent of progression through the mitotic cell cycle. |
| protein phosphorylation | The process of introducing a phosphate group on to a protein. |
| regulation of platelet aggregation | Any process that modulates the rate, frequency or extent of platelet aggregation. Platelet aggregation is the adhesion of one platelet to one or more other platelets via adhesion molecules. |
19 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 |
| P05126 | PRKCB | Protein kinase C beta type | Bos taurus (Bovine) | SS |
| A1A4I4 | PKN1 | Serine/threonine-protein kinase N1 | Bos taurus (Bovine) | SS |
| P05128 | PRKCG | Protein kinase C gamma type | Bos taurus (Bovine) | SS |
| A2VDV2 | STK38 | Serine/threonine-protein kinase 38 | 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 |
| P05129 | PRKCG | Protein kinase C gamma type | Homo sapiens (Human) | SS |
| P05771 | PRKCB | Protein kinase C beta type | Homo sapiens (Human) | SS |
| P17252 | PRKCA | Protein kinase C alpha type | Homo sapiens (Human) | EV |
| P68404 | Prkcb | Protein kinase C beta type | Mus musculus (Mouse) | SS |
| P63318 | Prkcg | Protein kinase C gamma type | Mus musculus (Mouse) | SS |
| P20444 | Prkca | Protein kinase C alpha type | Mus musculus (Mouse) | SS |
| P68403 | Prkcb | Protein kinase C beta type | Rattus norvegicus (Rat) | SS |
| P63319 | Prkcg | Protein kinase C gamma type | Rattus norvegicus (Rat) | SS |
| P05696 | Prkca | Protein kinase C alpha type | Rattus norvegicus (Rat) | SS |
| 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 |
| MADVFPAAEP | AAPQDVANRF | ARKGALRQKN | VHEVKNHRFI | ARFFKQPTFC | SHCTDFIWGF |
| 70 | 80 | 90 | 100 | 110 | 120 |
| GKQGFQCQVC | CFVVHKRCHE | FVTFSCPGAD | KGPDTDDPRS | KHKFKIHTYG | SPTFCDHCGS |
| 130 | 140 | 150 | 160 | 170 | 180 |
| LLYGLIHQGM | KCDTCDMNVH | KQCVINVPSL | CGMDHTEKRG | RIYLKAEVTD | EKLHVTVRDA |
| 190 | 200 | 210 | 220 | 230 | 240 |
| KNLIPMDPNG | LSDPYVKLKL | IPDPKNESKQ | KTKTIRSTLN | PRWDESFTFK | LKPSDKDRRL |
| 250 | 260 | 270 | 280 | 290 | 300 |
| SEEIWDWDRT | TRNDFMGSLS | FGVSELMKMP | ASGWYKLLNQ | EEGEYYNVPI | PEGDEEGNVE |
| 310 | 320 | 330 | 340 | 350 | 360 |
| LRQKFEKAKL | GPAGNKVISP | SEDRRQPSNN | LDRVKLTDFN | FLMVLGKGSF | GKVMLADRKG |
| 370 | 380 | 390 | 400 | 410 | 420 |
| TEELYAIKIL | KKDVVIQDDD | VECTMVEKRV | LALLDKPPFL | TQLHSCFQTV | DRLYFVMEYV |
| 430 | 440 | 450 | 460 | 470 | 480 |
| NGGDLMYHIQ | QVGKFKEPQA | VFYAAEISIG | LFFLHKRGII | YRDLKLDNVM | LDSEGHIKIA |
| 490 | 500 | 510 | 520 | 530 | 540 |
| DFGMCKEHMM | DGVTTRTFCG | TPDYIAPEII | AYQPYGKSVD | WWAYGVLLYE | MLAGQPPFDG |
| 550 | 560 | 570 | 580 | 590 | 600 |
| EDEDELFQSI | MEHNVSYPKS | LSKEAVSICK | GLMTKHPGKR | LGCGPEGERD | VREHAFFRRI |
| 610 | 620 | 630 | 640 | 650 | 660 |
| DWEKLENREI | QPPFKPKVCG | KGAENFDKFF | TRGQPVLTPP | DQLVIANIDQ | SDFEGFSYVN |
| 670 | |||||
| PQFVHPILQS | AV |