P28652
SS
Gene name |
Camk2b (Camk2d) |
Protein name |
Calcium/calmodulin-dependent protein kinase type II subunit beta |
Names |
CaM kinase II subunit beta , CaMK-II subunit beta , EC 2.7.11.17 |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:12323 |
EC number |
2.7.11.17: Protein-serine/threonine kinases |
Protein Class |
|
Descriptions
CaMKII is one of the most important transducers of Ca2+signals in a variety of cell types and is highly conserved across animal species. The calmodulin-responsive regulatory segment forms a coiled coil structure that blocks peptide and ATP binding to the otherwise intrinsically active kinase domain.Ca2+/CaM removes the autoinhibitory regulatory segment located C-terminal to the kinase domain which releases the catalytic activity of the enzyme.
Autoinhibitory domains (AIDs)
Target domain |
14-272 (Protein kinase domain) |
Relief mechanism |
Partner binding |
Assay |
|
Accessory elements
156-179 (Activation loop from InterPro)
Target domain |
14-272 (Protein kinase domain) |
Relief mechanism |
|
Assay |
|
References
- Rosenberg OS et al. (2005) "Structure of the autoinhibited kinase domain of CaMKII and SAXS analysis of the holoenzyme", Cell, 123, 849-60
- Rellos P et al. (2010) "Structure of the CaMKIIdelta/calmodulin complex reveals the molecular mechanism of CaMKII kinase activation", PLoS biology, 8, e1000426
- Akita T et al. (2018) "De novo variants in CAMK2A and CAMK2B cause neurodevelopmental disorders", Annals of clinical and translational neurology, 5, 280-296
- Morlot C et al. (2007) "Production of Slit2 LRR domains in mammalian cells for structural studies and the structure of human Slit2 domain 3", Acta crystallographica. Section D, Biological crystallography, 63, 961-8
- Yeon JH et al. (2016) "Systems-wide Identification of cis-Regulatory Elements in Proteins", Cell systems, 2, 89-100
- Yang E et al. (1999) "Structural examination of autoregulation of multifunctional calcium/calmodulin-dependent protein kinase II", The Journal of biological chemistry, 274, 26199-208
- Özden C et al. (2022) "CaMKII binds both substrates and activators at the active site", Cell reports, 40, 111064
Autoinhibited structure
Activated structure
1 structures for P28652
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-P28652-F1 | Predicted | AlphaFoldDB |
19 variants for P28652
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs3389143289 | 89 | V>F | No | EVA | |
| rs3389140842 | 95 | G>D | No | EVA | |
| rs3389105262 | 99 | F>V | No | EVA | |
| rs3389153208 | 105 | R>* | No | EVA | |
| rs3389139588 | 139 | P>S | No | EVA | |
| rs3389140704 | 158 | F>S | No | EVA | |
| rs3389081256 | 198 | W>R | No | EVA | |
| rs3389139582 | 209 | V>L | No | EVA | |
| rs3389081214 | 251 | Q>* | No | EVA | |
| rs3389140735 | 259 | K>T | No | EVA | |
| rs3389140930 | 269 | H>Y | No | EVA | |
| rs3389136872 | 296 | A>S | No | EVA | |
| rs3401593774 | 297 | R>S | No | EVA | |
| rs3401807303 | 316 | V>CPLLAPG* | No | EVA | |
| rs3389151680 | 326 | M>I | No | EVA | |
| rs3389114378 | 332 | G>S | No | EVA | |
| rs3389140739 | 369 | K>N | No | EVA | |
| rs3389140856 | 402 | I>L | No | EVA | |
| rs3389136912 | 509 | R>H | No | EVA |
No associated diseases with P28652
4 regional properties for P28652
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | Protein kinase domain | 14 - 272 | IPR000719 |
| active_site | Serine/threonine-protein kinase, active site | 132 - 144 | IPR008271 |
| domain | Calcium/calmodulin-dependent protein kinase II, association-domain | 410 - 537 | IPR013543 |
| binding_site | Protein kinase, ATP binding site | 20 - 43 | IPR017441 |
Functions
| Description | ||
|---|---|---|
| EC Number | 2.7.11.17 | Protein-serine/threonine kinases |
| Subcellular Localization |
|
|
| PANTHER Family | ||
| PANTHER Subfamily | ||
| PANTHER Protein Class | ||
| PANTHER Pathway Category | No pathway information available | |
10 GO annotations of cellular component
| Name | Definition |
|---|---|
| centrosome | A structure comprised of a core structure (in most organisms, a pair of centrioles) and peripheral material from which a microtubule-based structure, such as a spindle apparatus, is organized. Centrosomes occur close to the nucleus during interphase in many eukaryotic cells, though in animal cells it changes continually during the cell-division cycle. |
| 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. |
| glutamatergic synapse | A synapse that uses glutamate as a neurotransmitter. |
| neuron projection | A prolongation or process extending from a nerve cell, e.g. an axon or dendrite. |
| perikaryon | The portion of the cell soma (neuronal cell body) that excludes the nucleus. |
| 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. |
| sarcoplasmic reticulum membrane | The lipid bilayer surrounding the sarcoplasmic reticulum. |
| spindle midzone | The area in the center of the spindle where the spindle microtubules from opposite poles overlap. |
9 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 serine/threonine kinase activity | Calcium-dependent catalysis of the reactions |
| calmodulin binding | Binding to calmodulin, a calcium-binding protein with many roles, both in the calcium-bound and calcium-free states. |
| calmodulin-dependent protein kinase activity | Calmodulin-dependent catalysis of the reactions |
| 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 |
| protein serine/threonine kinase activity | Catalysis of the reactions |
| structural constituent of postsynaptic actin cytoskeleton | The action of a molecule that contributes to the structural integrity of a postsynaptic actin cytoskeleton. |
20 GO annotations of biological process
| Name | Definition |
|---|---|
| activation of meiosis involved in egg activation | Any process that starts the inactive process of meiosis in an egg after the egg has been fertilized or physiologically activated. Eggs generally arrest in meiosis and complete the process after activation. |
| apoptotic signaling pathway | The series of molecular signals which triggers the apoptotic death of a cell. The pathway starts with reception of a signal, and ends when the execution phase of apoptosis is triggered. |
| calcium ion transport | The directed movement of calcium (Ca) ions into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. |
| cell differentiation | The cellular developmental process in which a relatively unspecialized cell, e.g. embryonic or regenerative cell, acquires specialized structural and/or functional features that characterize a specific cell. Differentiation includes the processes involved in commitment of a cell to a specific fate and its subsequent development to the mature state. |
| cell projection morphogenesis | The process in which the anatomical structures of a cell projection are generated and organized. |
| G1/S transition of mitotic cell cycle | The mitotic cell cycle transition by which a cell in G1 commits to S phase. The process begins with the build up of G1 cyclin-dependent kinase (G1 CDK), resulting in the activation of transcription of G1 cyclins. The process ends with the positive feedback of the G1 cyclins on the G1 CDK which commits the cell to S phase, in which DNA replication is initiated. |
| 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. |
| nervous system development | The process whose specific outcome is the progression of nervous tissue over time, from its formation to its mature state. |
| neuromuscular process controlling balance | Any process that an organism uses to control its balance, the orientation of the organism (or the head of the organism) in relation to the source of gravity. In humans and animals, balance is perceived through visual cues, the labyrinth system of the inner ears and information from skin pressure receptors and muscle and joint receptors. |
| 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 apoptotic signaling pathway | Any process that activates or increases the frequency, rate or extent of apoptotic signaling pathway. |
| positive regulation of dendritic spine morphogenesis | Any process that increases the rate, frequency, or extent of dendritic spine morphogenesis, the process in which the anatomical structures of a dendritic spine are generated and organized. A dendritic spine is a protrusion from a dendrite and a specialized subcellular compartment involved in synaptic transmission. |
| positive regulation of neuron projection development | Any process that increases the rate, frequency or extent of neuron projection development. Neuron projection development is the process whose specific outcome is the progression of a neuron projection over time, from its formation to the mature structure. A neuron projection is any process extending from a neural cell, such as axons or dendrites (collectively called neurites). |
| positive regulation of synapse maturation | Any process that increases the extent of synapse maturation, the process that organizes a synapse so that it attains its fully functional state. |
| regulation of long-term neuronal synaptic plasticity | A process that modulates long-term neuronal synaptic plasticity, the ability of neuronal synapses to change long-term as circumstances require. Long-term neuronal synaptic plasticity generally involves increase or decrease in actual synapse numbers. |
| regulation of neuron migration | Any process that modulates the frequency, rate or extent of neuron migration. |
| regulation of protein localization to plasma membrane | Any process that modulates the frequency, rate or extent of protein localization to plasma membrane. |
| regulation of synapse maturation | Any process that modulates the extent of synapse maturation, the process that organizes a synapse so that it attains its fully functional state. |
| regulation of synaptic transmission, cholinergic | Any process that modulates the frequency, rate or extent of cholinergic synaptic transmission, the process of communication from a neuron to another neuron across a synapse using the neurotransmitter acetylcholine. |
| response to cadmium ion | 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 cadmium (Cd) ion stimulus. |
40 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| Q2HJF7 | CAMK2D | Calcium/calmodulin-dependent protein kinase type II subunit delta | Bos taurus (Bovine) | SS |
| Q3MHJ9 | CAMK2B | Calcium/calmodulin-dependent protein kinase type II subunit beta | Bos taurus (Bovine) | SS |
| Q5ZKI0 | CAMK2D | Calcium/calmodulin-dependent protein kinase type II delta chain | Gallus gallus (Chicken) | SS |
| Q24210 | CASK | Peripheral plasma membrane protein CASK | Drosophila melanogaster (Fruit fly) | SS |
| Q00168 | CaMKII | Calcium/calmodulin-dependent protein kinase type II alpha chain | Drosophila melanogaster (Fruit fly) | SS |
| Q13555 | CAMK2G | Calcium/calmodulin-dependent protein kinase type II subunit gamma | Homo sapiens (Human) | EV |
| O14936 | CASK | Peripheral plasma membrane protein CASK | Homo sapiens (Human) | EV |
| Q9UQM7 | CAMK2A | Calcium/calmodulin-dependent protein kinase type II subunit alpha | Homo sapiens (Human) | EV |
| Q13557 | CAMK2D | Calcium/calmodulin-dependent protein kinase type II subunit delta | Homo sapiens (Human) | EV |
| Q13554 | CAMK2B | Calcium/calmodulin-dependent protein kinase type II subunit beta | Homo sapiens (Human) | EV |
| O70589 | Cask | Peripheral plasma membrane protein CASK | Mus musculus (Mouse) | SS |
| P07934 | Phkg1 | Phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform | Mus musculus (Mouse) | SS |
| Q9DB30 | Phkg2 | Phosphorylase b kinase gamma catalytic chain, liver/testis isoform | Mus musculus (Mouse) | PR |
| P11798 | Camk2a | Calcium/calmodulin-dependent protein kinase type II subunit alpha | Mus musculus (Mouse) | PR |
| Q923T9 | Camk2g | Calcium/calmodulin-dependent protein kinase type II subunit gamma | Mus musculus (Mouse) | SS |
| Q6PHZ2 | Camk2d | Calcium/calmodulin-dependent protein kinase type II subunit delta | Mus musculus (Mouse) | SS |
| Q8VCR8 | Mylk2 | Myosin light chain kinase 2, skeletal/cardiac muscle | Mus musculus (Mouse) | SS |
| Q3UIZ8 | Mylk3 | Myosin light chain kinase 3 | Mus musculus (Mouse) | SS |
| Q91YA2 | Pskh1 | Serine/threonine-protein kinase H1 | Mus musculus (Mouse) | SS |
| Q9QYK9 | Pnck | Calcium/calmodulin-dependent protein kinase type 1B | Mus musculus (Mouse) | PR |
| Q91VB2 | Camk1g | Calcium/calmodulin-dependent protein kinase type 1G | Mus musculus (Mouse) | SS |
| Q8BW96 | Camk1d | Calcium/calmodulin-dependent protein kinase type 1D | Mus musculus (Mouse) | SS |
| Q3UHL1 | Camkv | CaM kinase-like vesicle-associated protein | Mus musculus (Mouse) | SS |
| Q91YS8 | Camk1 | Calcium/calmodulin-dependent protein kinase type 1 | Mus musculus (Mouse) | SS |
| Q95266 | CAMK2D | Calcium/calmodulin-dependent protein kinase type II subunit delta | Sus scrofa (Pig) | SS |
| P15791 | Camk2d | Calcium/calmodulin-dependent protein kinase type II subunit delta | Rattus norvegicus (Rat) | SS |
| P11275 | Camk2a | Calcium/calmodulin-dependent protein kinase type II subunit alpha | Rattus norvegicus (Rat) | PR |
| P11730 | Camk2g | Calcium/calmodulin-dependent protein kinase type II subunit gamma | Rattus norvegicus (Rat) | SS |
| P08413 | Camk2b | Calcium/calmodulin-dependent protein kinase type II subunit beta | Rattus norvegicus (Rat) | SS |
| P54936 | lin-2 | Protein lin-2 | Caenorhabditis elegans | SS |
| O62305 | unc-43 | Calcium/calmodulin-dependent protein kinase type II | Caenorhabditis elegans | EV |
| Q3E9C0 | CPK34 | Calcium-dependent protein kinase 34 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q9FMP5 | CPK17 | Calcium-dependent protein kinase 17 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q42479 | CPK3 | Calcium-dependent protein kinase 3 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q9ZSA4 | CPK27 | Calcium-dependent protein kinase 27 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q7XJR9 | CPK16 | Calcium-dependent protein kinase 16 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q1PE17 | CPK18 | Calcium-dependent protein kinase 18 | Arabidopsis thaliana (Mouse-ear cress) | SS |
| Q9FKW4 | CPK28 | Calcium-dependent protein kinase 28 | Arabidopsis thaliana (Mouse-ear cress) | SS |
| Q6DGS3 | camk2d2 | Calcium/calmodulin-dependent protein kinase type II delta 2 chain | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| Q6DEH3 | camk2d1 | Calcium/calmodulin-dependent protein kinase type II delta 1 chain | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MATTVTCTRF | TDEYQLYEDI | GKGAFSVVRR | CVKLCTGHEY | AAKIINTKKL | SARDHQKLER |
| 70 | 80 | 90 | 100 | 110 | 120 |
| EARICRLLKH | SNIVRLHDSI | SEEGFHYLVF | DLVTGGELFE | DIVAREYYSE | ADASHCIQQI |
| 130 | 140 | 150 | 160 | 170 | 180 |
| LEAVLHCHQM | GVVHRDLKPE | NLLLASKCKG | AAVKLADFGL | AIEVQGDQQA | WFGFAGTPGY |
| 190 | 200 | 210 | 220 | 230 | 240 |
| LSPEVLRKEA | YGKPVDIWAC | GVILYILLVG | YPPFWDEDQH | KLYQQIKAGA | YDFPSPEWDT |
| 250 | 260 | 270 | 280 | 290 | 300 |
| VTPEAKNLIN | QMLTINPAKR | ITAHEALKHP | WVCQRSTVAS | MMHRQETVEC | LKKFNARRKL |
| 310 | 320 | 330 | 340 | 350 | 360 |
| KGAILTTMLA | TRNFSVGRQT | TAPATMSTAA | SGTTMGLVEQ | AKSLLNKKAD | GVKPQTNSTK |
| 370 | 380 | 390 | 400 | 410 | 420 |
| NSSAITSPKG | SLPPAALEPQ | TTVIHNPVDG | IKESSDSTNT | TIEDEDAKAR | KQEIIKTTEQ |
| 430 | 440 | 450 | 460 | 470 | 480 |
| LIEAVNNGDF | EAYAKICDPG | LTSFEPEALG | NLVEGMDFHR | FYFENLLAKN | SKPIHTTILN |
| 490 | 500 | 510 | 520 | 530 | 540 |
| PHVHVIGEDA | ACIAYIRLTQ | YIDGQGRPRT | SQSEETRVWH | RRDGKWQNVH | FHCSGAPVAP |
| LQ |