(Calcium/calmodulin-dependent protein kinase type II subunit alpha) x 2
キーワード
SIGNALING PROTEIN / TRANSFERASE (転移酵素) / Calcium calmodulin dependent protein kinase II / holoenzyme (酵素) / splicing
機能・相同性
機能・相同性情報
peptidyl-threonine autophosphorylation / regulation of endocannabinoid signaling pathway / calcium- and calmodulin-dependent protein kinase complex / regulation of neuron migration / Ca2+/calmodulin-dependent protein kinase / regulation of neurotransmitter secretion / dendritic spine development / positive regulation of calcium ion transport / Trafficking of AMPA receptors / negative regulation of hydrolase activity ...peptidyl-threonine autophosphorylation / regulation of endocannabinoid signaling pathway / calcium- and calmodulin-dependent protein kinase complex / regulation of neuron migration / Ca2+/calmodulin-dependent protein kinase / regulation of neurotransmitter secretion / dendritic spine development / positive regulation of calcium ion transport / Trafficking of AMPA receptors / negative regulation of hydrolase activity / Assembly and cell surface presentation of NMDA receptors / regulation of mitochondrial membrane permeability involved in apoptotic process / 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 / regulation of neuronal synaptic plasticity / Phase 0 - rapid depolarisation / Ion transport by P-type ATPases / 長期増強 / 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 / calcium ion transport / Signaling by moderate kinase activity BRAF mutants / Paradoxical activation of RAF signaling by kinase inactive BRAF / Signaling downstream of RAS mutants / endocytic vesicle membrane / Interferon gamma signaling / Signaling by BRAF and RAF1 fusions / Ca2+ pathway / kinase activity / positive regulation of NF-kappaB transcription factor activity / RAF/MAP kinase cascade / peptidyl-serine phosphorylation / 樹状突起スパイン / protein autophosphorylation / postsynaptic density / calmodulin binding / neuron projection / protein phosphorylation / protein serine kinase activity / protein serine/threonine kinase activity / protein homodimerization activity / ミトコンドリア / 核質 / ATP binding / identical protein binding / metal ion binding / 細胞核 / 細胞質基質 / 細胞質 類似検索 - 分子機能
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. / Protein kinase domain / Serine/Threonine protein kinases, catalytic 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. / Protein kinase domain / Serine/Threonine protein kinases, catalytic domain / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily 類似検索 - ドメイン・相同性
Calcium/calmodulin-dependent protein kinase type II subunit alpha 類似検索 - 構成要素
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01GM123157
米国
引用
ジャーナル: Sci Signal / 年: 2020 タイトル: Heterogeneity in human hippocampal CaMKII transcripts reveals allosteric hub-dependent regulation. 著者: 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 / 要旨: 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.
#195 - 2016年3月 RAFタンパク質キナーゼ (RAF Protein Kinases) 類似性 (1)
-
集合体
登録構造単位
A: Calcium/calmodulin-dependent protein kinase type II subunit alpha B: Calcium/calmodulin-dependent protein kinase type II subunit alpha C: Calcium/calmodulin-dependent protein kinase type II subunit alpha D: Calcium/calmodulin-dependent protein kinase type II subunit alpha E: Calcium/calmodulin-dependent protein kinase type II subunit alpha F: Calcium/calmodulin-dependent protein kinase type II subunit alpha G: Calcium/calmodulin-dependent protein kinase type II subunit alpha I: Calcium/calmodulin-dependent protein kinase type II subunit alpha J: Calcium/calmodulin-dependent protein kinase type II subunit alpha K: Calcium/calmodulin-dependent protein kinase type II subunit alpha L: Calcium/calmodulin-dependent protein kinase type II subunit alpha M: Calcium/calmodulin-dependent protein kinase type II subunit alpha O: Calcium/calmodulin-dependent protein kinase type II subunit alpha