CAMK1

Calcium/calmodulin-dependent protein kinase I is expressed in many tissues and is a component of a calmodulin-dependent protein kinase cascade. Calcium/calmodulin directly activates calcium/calmodulin-dependent protein kinase I by binding to the enzyme and indirectly promotes the phosphorylation and synergistic activation of the enzyme by calcium/calmodulin-dependent protein kinase I kinase. [provided by RefSeq]

calcium/calmodulin-dependent protein kinase I

Calcium/calmodulin-dependent protein kinase that operates in the calcium-triggered CaMKK-CaMK1 signaling cascade and, upon calcium influx, regulates transcription activators activity, cell cycle, hormone production, cell differentiation, actin filament organization and neurite outgrowth. Recognizes the substrate consensus sequence [MVLIF]-x-R-x2-[ST]-x3-[MVLIF]. Regulates axonal extension and growth cone motility in hippocampal and cerebellar nerve cells. Upon NMDA receptor-mediated Ca2+ elevation, promotes dendritic growth in hippocampal neurons and is essential in synapses for full long-term potentiation (LTP) and ERK2-dependent translational activation. Downstream of NMDA receptors, promotes the formation of spines and synapses in hippocampal neurons by phosphorylating ARHGEF7/BETAPIX on 'Ser-694', which results in the enhancement of ARHGEF7 activity and activation of RAC1. Promotes neuronal differentiation and neurite outgrowth by activation and phosphorylation of MARK2 on 'Ser-91', 'Ser-92', 'Ser-93' and 'Ser-294'. Promotes nuclear export of HDAC5 and binding to 14-3-3 by phosphorylation of 'Ser-259' and 'Ser-498' in the regulation of muscle cell differentiation. Regulates NUMB-mediated endocytosis by phosphorylation of NUMB on 'Ser-276' and 'Ser-295'. Involved in the regulation of basal and estrogen-stimulated migration of medulloblastoma cells through ARHGEF7/BETAPIX phosphorylation (By similarity).

Is required for proper activation of cyclin-D1/CDK4 complex during G1 progression in diploid fibroblasts. Plays a role in K+ and ANG2-mediated regulation of the aldosterone synthase (CYP11B2) to produce aldosterone in the adrenal cortex. Phosphorylates EIF4G3/eIF4GII. In vitro phosphorylates CREB1, ATF1, CFTR, MYL9 and SYN1/synapsin I.

Cell cycle Source: UniProtKB-KW
Cell differentiation Source: UniProtKB-KW
Chemical synaptic transmission Source: Reactome
Negative regulation of protein binding Source: UniProtKB
Nervous system development Source: UniProtKB-KW
Nucleocytoplasmic transport Source: Ensembl
Peptidyl-serine phosphorylation Source: GO_Central
Positive regulation of dendritic spine development Source: UniProtKB
Positive regulation of muscle cell differentiation Source: BHF-UCL
Positive regulation of neuron projection development Source: UniProtKB
Positive regulation of peptidyl-serine phosphorylation Source: UniProtKB
Positive regulation of protein acetylation Source: UniProtKB
Positive regulation of protein export from nucleus Source: UniProtKB
Positive regulation of protein serine/threonine kinase activity Source: UniProtKB
Positive regulation of synapse structural plasticity Source: UniProtKB
Positive regulation of syncytium formation by plasma membrane fusion Source: UniProtKB
Positive regulation of transcription by RNA polymerase II Source: UniProtKB
Protein phosphorylation Source: UniProtKB
Regulation of muscle cell differentiation Source: UniProtKB
Regulation of protein binding Source: UniProtKB
Regulation of protein localization Source: UniProtKB
Signal transduction Source: ProtInc

Nucleus; Cytoplasm. Predominantly cytoplasmic.

Phosphorylated by CaMKK1 and CaMKK2 on Thr-177.
Polybiquitinated by the E3 ubiquitin-protein ligase complex SCF(FBXL12), leading to proteasomal degradation.