P15791
SS
Gene name |
Camk2d |
Protein name |
Calcium/calmodulin-dependent protein kinase type II subunit delta |
Names |
CaM kinase II subunit delta , CaMK-II subunit delta , EC 2.7.11.17 |
Species |
Rattus norvegicus (Rat) |
KEGG Pathway |
rno:24246 |
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 P15791
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-P15791-F1 | Predicted | AlphaFoldDB |
No variants for P15791
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| No variants for P15791 | |||||
No associated diseases with P15791
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 | |
13 GO annotations of cellular component
| Name | Definition |
|---|---|
| axon initial segment | Portion of the axon proximal to the neuronal cell body, at the level of the axon hillock. The action potentials that propagate along the axon are generated at the level of this initial segment. |
| calcium- and calmodulin-dependent protein kinase complex | An enzyme complex which in eukaryotes is composed of four different chains |
| cytoplasm | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. |
| intercalated disc | A complex cell-cell junction at which myofibrils terminate in cardiomyocytes; mediates mechanical and electrochemical integration between individual cardiomyocytes. The intercalated disc contains regions of tight mechanical attachment (fasciae adherentes and desmosomes) and electrical coupling (gap junctions) between adjacent cells. |
| neuromuscular junction | The junction between the axon of a motor neuron and a muscle fiber. In response to the arrival of action potentials, the presynaptic button releases molecules of neurotransmitters into the synaptic cleft. These diffuse across the cleft and transmit the signal to the postsynaptic membrane of the muscle fiber, leading to a change in post-synaptic potential. |
| neuron projection | A prolongation or process extending from a nerve cell, e.g. an axon or dendrite. |
| neuronal cell body | The portion of a neuron that includes the nucleus, but excludes cell projections such as axons and dendrites. |
| 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. |
| protein-containing complex | A stable assembly of two or more macromolecules, i.e. proteins, nucleic acids, carbohydrates or lipids, in which at least one component is a protein and the constituent parts function together. |
| sarcoplasmic reticulum | A fine reticular network of membrane-limited elements that pervades the sarcoplasm of a muscle cell; continuous over large portions of the cell and with the nuclear envelope; that part of the endoplasmic reticulum specialized for calcium release, uptake and storage. |
| sarcoplasmic reticulum membrane | The lipid bilayer surrounding the sarcoplasmic reticulum. |
| T-tubule | Invagination of the plasma membrane of a muscle cell that extends inward from the cell surface around each myofibril. The ends of T-tubules make contact with the sarcoplasmic reticulum membrane. |
12 GO annotations of molecular function
| Name | Definition |
|---|---|
| ATP binding | Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator. |
| 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 |
| identical protein binding | Binding to an identical protein or proteins. |
| nitric-oxide synthase binding | Binding to nitric-oxide synthase. |
| protein homodimerization activity | Binding to an identical protein to form a homodimer. |
| protein kinase activity | Catalysis of the phosphorylation of an amino acid residue in a protein, usually according to the reaction |
| protein serine kinase activity | Catalysis of the reactions |
| protein serine/threonine kinase activity | Catalysis of the reactions |
| sodium channel inhibitor activity | Binds to and stops, prevents, or reduces the activity of a sodium channel. |
| titin binding | Binding to titin, any of a family of giant proteins found in striated and smooth muscle. In striated muscle, single titin molecules span half the sarcomere, with their N- and C-termini in the Z-disc and M-line, respectively. |
| transmembrane transporter binding | Binding to a transmembrane transporter, a protein or protein complex that enables the transfer of a substance, usually a specific substance or a group of related substances, from one side of a membrane to the other. |
33 GO annotations of biological process
| Name | Definition |
|---|---|
| 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. |
| cardiac muscle cell contraction | The actin filament-based process in which cytoplasmic actin filaments slide past one another resulting in contraction of a cardiac muscle cell. |
| cardiac muscle contraction | Muscle contraction of cardiac muscle tissue. |
| cell growth involved in cardiac muscle cell development | The growth of a cardiac muscle cell, where growth contributes to the progression of the cell over time from its initial formation to its mature state. |
| endoplasmic reticulum calcium ion homeostasis | Any process involved in the maintenance of an internal steady state of calcium ions within the endoplasmic reticulum of a cell or between the endoplasmic reticulum and its surroundings. |
| 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. |
| intracellular potassium ion homeostasis | A homeostatic process involved in the maintenance of a steady state level of potassium ions within a cell. |
| negative regulation of sodium ion transmembrane transport | Any process that stops, prevents or reduces the frequency, rate or extent of sodium ion transmembrane transport. |
| 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 cardiac muscle cell apoptotic process | Any process that increases 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. |
| 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 DNA biosynthetic process | Any process that activates or increases the frequency, rate or extent of DNA biosynthetic process. |
| 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 G2/M transition of mitotic cell cycle | Any signalling pathway that activates or increases the activity of a cell cycle cyclin-dependent protein kinase to modulate the switch from G2 phase to M phase of the mitotic cell cycle. |
| positive regulation of Rac protein signal transduction | Any process that activates or increases the frequency, rate or extent of Rac protein signal transduction. |
| positive regulation of smooth muscle cell migration | Any process that activates, maintains or increases the frequency, rate or extent of smooth muscle cell migration. |
| positive regulation of vascular associated smooth muscle cell proliferation | Any process that activates or increases the frequency, rate or extent of vascular smooth muscle cell proliferation. |
| protein phosphorylation | The process of introducing a phosphate group on to a protein. |
| regulation of calcium ion transmembrane transport via high voltage-gated calcium channel | Any process that modulates the frequency, rate or extent of generation of calcium ion transmembrane transport via high voltage-gated calcium channel. |
| regulation of cardiac muscle cell action potential | Any process that modulates the frequency, rate or extent of action potential creation, propagation or termination in a cardiac muscle cell. This typically occurs via modulation of the activity or expression of voltage-gated ion channels. |
| regulation of cardiac muscle cell action potential involved in regulation of contraction | Any process that modulates the frequency, rate or extent of action potential creation, propagation or termination in a cardiac muscle cell contributing to the regulation of its contraction. |
| regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion | Any process that modulates the frequency, rate or extent of cardiac muscle contraction via the regulation of the release of sequestered calcium ion by sarcoplasmic reticulum into cytosol. The sarcoplasmic reticulum is the endoplasmic reticulum of striated muscle, specialised for the sequestration of calcium ions that are released upon receipt of a signal relayed by the T tubules from the neuromuscular junction. |
| regulation of cell communication by electrical coupling | Any process that modulates the frequency, rate or extent of cell communication via electrical coupling. Cell communication via electrical coupling is the process that mediates signaling interactions between one cell and another cell by transfer of current between their adjacent cytoplasms via intercellular protein channels. |
| regulation of cell communication by electrical coupling involved in cardiac conduction | Any process that modulates the frequency, rate or extent of cell communication by electrical coupling involved in cardiac conduction. |
| regulation of cellular localization | Any process that modulates the frequency, rate or extent of a process in which a cell, a substance, or a cellular entity is transported to, or maintained in a specific location within or in the membrane of a cell. |
| regulation of membrane depolarization | Any process that modulates the rate, frequency or extent of membrane depolarization. Membrane depolarization is the process in which membrane potential changes in the depolarizing direction from the resting potential, usually from negative to positive. |
| regulation of protein localization to plasma membrane | Any process that modulates the frequency, rate or extent of protein localization to plasma membrane. |
| regulation of relaxation of cardiac muscle | Any process that modulates the frequency, rate or extent of relaxation of cardiac muscle. |
| regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum | Any process that modulates the rate, frequency or extent of release of sequestered calcium ion into cytosol by the sarcoplasmic reticulum, the process in which the release of sequestered calcium ion by sarcoplasmic reticulum into cytosol occurs via calcium release channels. |
| regulation of sodium ion transport | Any process that modulates the frequency, rate or extent of the directed movement of sodium ions (Na+) into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. |
| relaxation of cardiac muscle | The process in which the extent of cardiac muscle contraction is reduced. |
| response to hypoxia | 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 stimulus indicating lowered oxygen tension. Hypoxia, defined as a decline in O2 levels below normoxic levels of 20.8 - 20.95%, results in metabolic adaptation at both the cellular and organismal level. |
49 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| Q3MHJ9 | CAMK2B | Calcium/calmodulin-dependent protein kinase type II subunit beta | Bos taurus (Bovine) | SS |
| Q2HJF7 | CAMK2D | Calcium/calmodulin-dependent protein kinase type II subunit delta | 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 |
| Q13554 | CAMK2B | Calcium/calmodulin-dependent protein kinase type II subunit beta | 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 |
| O70589 | Cask | Peripheral plasma membrane protein CASK | Mus musculus (Mouse) | SS |
| Q923T9 | Camk2g | Calcium/calmodulin-dependent protein kinase type II subunit gamma | Mus musculus (Mouse) | SS |
| P11798 | Camk2a | Calcium/calmodulin-dependent protein kinase type II subunit alpha | Mus musculus (Mouse) | PR |
| P28652 | Camk2b | Calcium/calmodulin-dependent protein kinase type II subunit beta | Mus musculus (Mouse) | SS |
| Q6PHZ2 | Camk2d | Calcium/calmodulin-dependent protein kinase type II subunit delta | Mus musculus (Mouse) | SS |
| Q95266 | CAMK2D | Calcium/calmodulin-dependent protein kinase type II subunit delta | Sus scrofa (Pig) | SS |
| P13286 | Phkg1 | Phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform | Rattus norvegicus (Rat) | SS |
| P31325 | Phkg2 | Phosphorylase b kinase gamma catalytic chain, liver/testis isoform | Rattus norvegicus (Rat) | PR |
| P08413 | Camk2b | Calcium/calmodulin-dependent protein kinase type II subunit beta | 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 |
| P20689 | Mylk2 | Myosin light chain kinase 2, skeletal/cardiac muscle | Rattus norvegicus (Rat) | SS |
| E9PT87 | Mylk3 | Myosin light chain kinase 3 | Rattus norvegicus (Rat) | SS |
| O70150 | Pnck | Calcium/calmodulin-dependent protein kinase type 1B | Rattus norvegicus (Rat) | PR |
| Q7TNJ7 | Camk1g | Calcium/calmodulin-dependent protein kinase type 1G | Rattus norvegicus (Rat) | SS |
| Q63092 | Camkv | CaM kinase-like vesicle-associated protein | Rattus norvegicus (Rat) | SS |
| Q63450 | Camk1 | Calcium/calmodulin-dependent protein kinase type 1 | Rattus norvegicus (Rat) | EV |
| Q75GE8 | CPK8 | Calcium-dependent protein kinase 8 | Oryza sativa subsp. japonica (Rice) | SS |
| Q6I5I8 | CPK16 | Calcium-dependent protein kinase 16 | Oryza sativa subsp. japonica (Rice) | SS |
| Q84SL0 | CPK20 | Calcium-dependent protein kinase 20 | Oryza sativa subsp. japonica (Rice) | SS |
| Q8LPZ7 | CPK3 | Calcium-dependent protein kinase 3 | Oryza sativa subsp. japonica (Rice) | SS |
| P54936 | lin-2 | Protein lin-2 | Caenorhabditis elegans | SS |
| O62305 | unc-43 | Calcium/calmodulin-dependent protein kinase type II | Caenorhabditis elegans | EV |
| Q9SSF8 | CPK30 | Calcium-dependent protein kinase 30 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q9M9V8 | CPK10 | Calcium-dependent protein kinase 10 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q8W4I7 | CPK13 | Calcium-dependent protein kinase 13 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q9SIQ7 | CPK24 | Calcium-dependent protein kinase 24 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| 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 |
| P93759 | GK-1 | Calcium-dependent protein kinase 14 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q6NLQ6 | CPK32 | Calcium-dependent protein kinase 32 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q38873 | CPK7 | Calcium-dependent protein kinase 7 | 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 |
| Q6DEH3 | camk2d1 | Calcium/calmodulin-dependent protein kinase type II delta 1 chain | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| Q6DGS3 | camk2d2 | Calcium/calmodulin-dependent protein kinase type II delta 2 chain | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MASTTTCTRF | TDEYQLFEEL | GKGAFSVVRR | CMKIPTGQEY | AAKIINTKKL | SARDHQKLER |
| 70 | 80 | 90 | 100 | 110 | 120 |
| EARICRLLKH | PNIVRLHDSI | SEEGFHYLVF | DLVTGGELFE | DIVAREYYSE | ADASHCIQQI |
| 130 | 140 | 150 | 160 | 170 | 180 |
| LESVNHCHLN | GIVHRDLKPE | NLLLASKSKG | AAVKLADFGL | AIEVQGDQQA | WFGFAGTPGY |
| 190 | 200 | 210 | 220 | 230 | 240 |
| LSPEVLRKDP | YGKPVDMWAC | GVILYILLVG | YPPFWDEDQH | RLYQQIKAGA | YDFPSPEWDT |
| 250 | 260 | 270 | 280 | 290 | 300 |
| VTPEAKDLIN | KMLTINPAKR | ITASEALKHP | WICQRSTVAS | MMHRQETVDC | LKKFNARRKL |
| 310 | 320 | 330 | 340 | 350 | 360 |
| KGAILTTMLA | TRNFSAAKSL | LKKPDGVKIN | NKANVVTSPK | ENIPTPALEP | QTTVIHNPDG |
| 370 | 380 | 390 | 400 | 410 | 420 |
| NKESTESSNT | TIEDEDVKAR | KQEIIKVTEQ | LIEAINNGDF | EAYTKICDPG | LTAFEPEALG |
| 430 | 440 | 450 | 460 | 470 | 480 |
| NLVEGMDFHR | FYFENALPKI | NKPIHTIILN | PHVHLVGDDA | ACIAYIRLTQ | YMDGNGMPKT |
| 490 | 500 | 510 | 520 | 530 | |
| MQSEETRVWH | RRDGKWQNIH | FHRSGSPTVP | IKPPCIPNGK | ENFSGGTSLW | QNI |