Protein or peptide: Calcium/calmodulin-dependent protein kinase type II subunit alpha
Protein or peptide: Calcium/calmodulin-dependent protein kinase type II subunit alpha
Keywords
Calcium calmodulin dependent protein kinase II / holoenzyme / splicing / SIGNALING PROTEIN / TRANSFERASE
Function / homology
Function and homology information
peptidyl-threonine autophosphorylation / regulation of endocannabinoid signaling pathway / calcium- and calmodulin-dependent protein kinase complex / Ca2+/calmodulin-dependent protein kinase / regulation of neurotransmitter secretion / regulation of neuron migration / dendritic spine development / Trafficking of AMPA receptors / positive regulation of calcium ion transport / negative regulation of hydrolase activity ...peptidyl-threonine autophosphorylation / regulation of endocannabinoid signaling pathway / calcium- and calmodulin-dependent protein kinase complex / Ca2+/calmodulin-dependent protein kinase / regulation of neurotransmitter secretion / regulation of neuron migration / dendritic spine development / Trafficking of AMPA receptors / positive regulation of calcium ion transport / negative regulation of hydrolase activity / Assembly and cell surface presentation of NMDA receptors / regulation of mitochondrial membrane permeability involved in apoptotic process / calcium/calmodulin-dependent protein kinase activity / CaMK IV-mediated phosphorylation of CREB / positive regulation of cardiac muscle cell apoptotic process / Negative regulation of NMDA receptor-mediated neuronal transmission / Unblocking of NMDA receptors, glutamate binding and activation / Phase 0 - rapid depolarisation / regulation of neuronal synaptic plasticity / Ion transport by P-type ATPases / Long-term potentiation / Regulation of MECP2 expression and activity / HSF1-dependent transactivation / cellular response to interferon-beta / glutamate receptor binding / Ion homeostasis / Ras activation upon Ca2+ influx through NMDA receptor / response to ischemia / angiotensin-activated signaling pathway / RAF activation / positive regulation of receptor signaling pathway via JAK-STAT / G1/S transition of mitotic cell cycle / cellular response to type II interferon / Signaling by RAF1 mutants / Signaling by moderate kinase activity BRAF mutants / Paradoxical activation of RAF signaling by kinase inactive BRAF / Signaling downstream of RAS mutants / calcium ion transport / endocytic vesicle membrane / Interferon gamma signaling / Signaling by BRAF and RAF1 fusions / kinase activity / Ca2+ pathway / positive regulation of NF-kappaB transcription factor activity / peptidyl-serine phosphorylation / RAF/MAP kinase cascade / protein autophosphorylation / dendritic spine / calmodulin binding / postsynaptic density / neuron projection / protein phosphorylation / protein serine kinase activity / protein serine/threonine kinase activity / protein homodimerization activity / mitochondrion / nucleoplasm / ATP binding / identical protein binding / nucleus / metal ion binding / cytoplasm / cytosol Similarity search - Function
Calcium/calmodulin-dependent protein kinase II, association-domain / Calcium/calmodulin dependent protein kinase II association domain / NTF2-like domain superfamily / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Serine/Threonine protein kinases, catalytic domain / Protein kinase domain / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. ...Calcium/calmodulin-dependent protein kinase II, association-domain / Calcium/calmodulin dependent protein kinase II association domain / NTF2-like domain superfamily / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Serine/Threonine protein kinases, catalytic domain / Protein kinase domain / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily Similarity search - Domain/homology
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01GM123157
United States
Citation
Journal: Sci Signal / Year: 2020 Title: Heterogeneity in human hippocampal CaMKII transcripts reveals allosteric hub-dependent regulation. Authors: Roman Sloutsky / Noelle Dziedzic / Matthew J Dunn / Rachel M Bates / Ana P Torres-Ocampo / Sivakumar Boopathy / Brendan Page / John G Weeks / Luke H Chao / Margaret M Stratton / Abstract: Calcium/calmodulin-dependent protein kinase II (CaMKII) plays a central role in Ca signaling throughout the body. In the hippocampus, CaMKII is required for learning and memory. Vertebrate genomes ...Calcium/calmodulin-dependent protein kinase II (CaMKII) plays a central role in Ca signaling throughout the body. In the hippocampus, CaMKII is required for learning and memory. Vertebrate genomes encode four CaMKII homologs: CaMKIIα, CaMKIIβ, CaMKIIγ, and CaMKIIδ. All CaMKIIs consist of a kinase domain, a regulatory segment, a variable linker region, and a hub domain, which is responsible for oligomerization. The four proteins differ primarily in linker length and composition because of extensive alternative splicing. Here, we report the heterogeneity of CaMKII transcripts in three complex samples of human hippocampus using deep sequencing. We showed that hippocampal cells contain a diverse collection of over 70 CaMKII transcripts from all four CaMKII-encoding genes. We characterized the Ca/CaM sensitivity of hippocampal CaMKII variants spanning a broad range of linker lengths and compositions. The effect of the variable linker on Ca/CaM sensitivity depended on the kinase and hub domains. Moreover, we revealed a previously uncharacterized role for the hub domain as an allosteric regulator of kinase activity, which may provide a pharmacological target for modulating CaMKII activity. Using small-angle x-ray scattering and single-particle cryo-electron microscopy (cryo-EM), we present evidence for extensive interactions between the kinase and the hub domains, even in the presence of a 30-residue linker. Together, these data suggest that Ca/CaM sensitivity in CaMKII is homolog dependent and includes substantial contributions from the hub domain. Our sequencing approach, combined with biochemistry, provides insights into understanding the complex pool of endogenous CaMKII splice variants.
History
Deposition
Mar 11, 2020
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Header (metadata) release
Jul 15, 2020
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Map release
Jul 15, 2020
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Update
Mar 6, 2024
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Current status
Mar 6, 2024
Processing site: RCSB / Status: Released
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Structure visualization
Movie
Surface view with section colored by density value
Macromolecule #1: Calcium/calmodulin-dependent protein kinase type II subunit alpha
Macromolecule
Name: Calcium/calmodulin-dependent protein kinase type II subunit alpha type: protein_or_peptide / ID: 1 / Number of copies: 12 / Enantiomer: LEVO / EC number: Ca2+/calmodulin-dependent protein kinase
UniProtKB: Calcium/calmodulin-dependent protein kinase type II subunit alpha
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Macromolecule #2: Calcium/calmodulin-dependent protein kinase type II subunit alpha
Macromolecule
Name: Calcium/calmodulin-dependent protein kinase type II subunit alpha type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO / EC number: Ca2+/calmodulin-dependent protein kinase
UniProtKB: Calcium/calmodulin-dependent protein kinase type II subunit alpha
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Experimental details
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Structure determination
Method
cryo EM
Processing
single particle reconstruction
Aggregation state
particle
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Sample preparation
Buffer
pH: 8
Grid
Model: C-flat-1.2/1.3 / Material: GOLD / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 30 sec. / Details: 30 mA for 30 s using PELCO easiGlow
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