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| Aliases | NCS1 , FLUP, FREQ, neuronal calcium sensor 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 603315 MGI: 109166 HomoloGene: 5719 GeneCards: NCS1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Neuronal calcium sensor-1 (NCS-1) also known as frequenin homolog (Drosophila) (freq) is a protein that is encoded by the FREQ gene in humans. [5] NCS-1 is a member of the neuronal calcium sensor family, [6] a class of EF hand containing calcium-myristoyl-switch proteins. [7]
NCS-1 regulates synaptic transmission, [8] helps control the dynamics of nerve terminal growth, [9] [10] [8] is critical for some forms of learning and memory in C. elegans [11] and mammals, [12] regulates corticohippocampal plasticity; and enhancing levels of NCS-1 in the mouse dentate gyrus increases spontaneous exploration of safe environments, [12] potentially linking NCS-1 to curiosity. [13]
NCS-1 is a calcium sensor, not a calcium buffer (chelator); thus it is a high-affinity, low-capacity, calcium-binding protein.
Frq can substitute for calmodulin in some situations. It is thought to be associated with neuronal secretory vesicles and regulate neurosecretion.
NCS-1 is a globular protein consisting of ten alpha-helices. Four pairs of alpha-helices each form independent 12-amino-acid loops containing a negatively charged calcium binding domain known as an EF-hand. However, only three of these EF hands are functional (the most N-terminal EF-hand does not bind calcium). They could be occupied not only by calcium but also by magnesium and zinc ions. [17] NCS-1 also contains at least two known protein binding domains, and a large surface exposed hydrophobic crevice containing EF-hands three and four. There is a myristoylation motif at the N-terminus that presumably allows NCS-1 to associate with lipid membranes.
The expression of NCS-1 increases in bipolar disorder and some forms of schizophrenia [18] and decreases in inflammatory bowel disease. [19] NCS-1 has also been linked with Autism. [20] In addition NCS-1 is significant in intelligence in creating curiosity by its function on dopamine D2 receptors in the dentate gyrus, increasing memory for complex tasks. [21]
NCS-1 was originally discovered in Drosophila as a gain-of-function mutation associated with frequency-dependent increases in neurotransmission. [22] A role in neurotransmission was later confirmed in Drosophila using frq null mutants. [8] Work in bovine chromaffin cells demonstrated that NCS-1 is also a modulator of neurotransmission in mammals. [23] The designation 'NCS-1' came from the assumption that the protein was expressed only in neuronal cell types, which is not the case. [24]
Calmodulin (CaM) (an abbreviation for calcium-modulated protein) is a multifunctional intermediate calcium-binding messenger protein expressed in all eukaryotic cells. It is an intracellular target of the secondary messenger Ca2+, and the binding of Ca2+ is required for the activation of calmodulin. Once bound to Ca2+, calmodulin acts as part of a calcium signal transduction pathway by modifying its interactions with various target proteins such as kinases or phosphatases.
BK channels (big potassium), are large conductance calcium-activated potassium channels, also known as Maxi-K, slo1, or Kca1.1. BK channels are voltage-gated potassium channels that conduct large amounts of potassium ions (K+) across the cell membrane, hence their name, big potassium. These channels can be activated (opened) by either electrical means, or by increasing Ca2+ concentrations in the cell. BK channels help regulate physiological processes, such as circadian behavioral rhythms and neuronal excitability. BK channels are also involved in many processes in the body, as it is a ubiquitous channel. They have a tetrameric structure that is composed of a transmembrane domain, voltage sensing domain, potassium channel domain, and a cytoplasmic C-terminal domain, with many X-ray structures for reference. Their function is to repolarize the membrane potential by allowing for potassium to flow outward, in response to a depolarization or increase in calcium levels.
CREB-TF is a cellular transcription factor. It binds to certain DNA sequences called cAMP response elements (CRE), thereby increasing or decreasing the transcription of the genes. CREB was first described in 1987 as a cAMP-responsive transcription factor regulating the somatostatin gene.
Calcium signaling is the use of calcium ions (Ca2+) to communicate and drive intracellular processes often as a step in signal transduction. Ca2+ is important for cellular signalling, for once it enters the cytosol of the cytoplasm it exerts allosteric regulatory effects on many enzymes and proteins. Ca2+ can act in signal transduction resulting from activation of ion channels or as a second messenger caused by indirect signal transduction pathways such as G protein-coupled receptors.
Glutamate receptors are synaptic and non synaptic receptors located primarily on the membranes of neuronal and glial cells. Glutamate is abundant in the human body, but particularly in the nervous system and especially prominent in the human brain where it is the body's most prominent neurotransmitter, the brain's main excitatory neurotransmitter, and also the precursor for GABA, the brain's main inhibitory neurotransmitter. Glutamate receptors are responsible for the glutamate-mediated postsynaptic excitation of neural cells, and are important for neural communication, memory formation, learning, and regulation.
Synaptotagmins (SYTs) constitute a family of membrane-trafficking proteins that are characterized by an N-terminal transmembrane region (TMR), a variable linker, and two C-terminal C2 domains - C2A and C2B. There are 17 isoforms in the mammalian synaptotagmin family. There are several C2-domain containing protein families that are related to synaptotagmins, including transmembrane (Ferlins, Extended-Synaptotagmin (E-Syt) membrane proteins, and MCTPs) and soluble (RIMS1 and RIMS2, UNC13D, synaptotagmin-related proteins and B/K) proteins. The family includes synaptotagmin 1, a Ca2+ sensor in the membrane of the pre-synaptic axon terminal, coded by gene SYT1.
Hippocalcin is a protein that in humans is encoded by the HPCA gene.
Ca2+
/calmodulin-dependent protein kinase II is a serine/threonine-specific protein kinase that is regulated by the Ca2+
/calmodulin complex. CaMKII is involved in many signaling cascades and is thought to be an important mediator of learning and memory. CaMKII is also necessary for Ca2+
homeostasis and reuptake in cardiomyocytes, chloride transport in epithelia, positive T-cell selection, and CD8 T-cell activation.
Neurocalcin is a neuronal calcium-binding protein that belongs to the neuronal calcium sensor (NCS) family of proteins. It expressed in mammalian brains. It possesses a Ca2+/myristoyl switch
Neuronal Calcium Sensor is a large family of proteins which work as calcium dependent molecular switches and includes members like Frequenin (NCS1), recoverin, GCAP, neurocalcin, visinin etc. All the members carry 4 EF hand motifs and an N-myristoyl group.
The L-type calcium channel is part of the high-voltage activated family of voltage-dependent calcium channel. "L" stands for long-lasting referring to the length of activation. This channel has four isoforms: Cav1.1, Cav1.2, Cav1.3, and Cav1.4.
Calsenilin is a protein that in humans is encoded by the KCNIP3 gene.
Visinin-like protein 1 is a protein that in humans is encoded by the VSNL1 gene.
Hippocalcin-like protein 1 is a protein that in humans is encoded by the HPCAL1 gene.
Calcium binding protein 1 is a protein that in humans is encoded by the CABP1 gene. Calcium-binding protein 1 is a calcium-binding protein discovered in 1999. It has two EF hand motifs and is expressed in neuronal cells in such areas as hippocampus, habenular nucleus of the epithalamus, Purkinje cell layer of the cerebellum, and the amacrine cells and cone bipolar cells of the retina.
DnaJ homolog subfamily C member 5, also known as cysteine string protein or CSP is a protein, that in humans encoded by the DNAJC5 gene. It was first described in 1990.
Kv channel-interacting protein 1 also known as KChIP1 is a protein that in humans is encoded by the KCNIP1 gene.
Kv channel-interacting protein 4 is a protein that in humans is encoded by the KCNIP4 gene.
Kv channel interacting proteins are members of a family of voltage-gated potassium (Kv) channel-interacting proteins, which belong to the recoverin branch of the EF-hand superfamily. Members of the KCNIP family are small calcium binding proteins. They all have EF-hand-like domains, and differ from each other in the N-terminus. They are integral subunit components of native Kv4 channel complexes. They may regulate A-type currents, and hence neuronal excitability, in response to changes in intracellular calcium. Alternative splicing results in multiple transcript variant encoding different isoforms.
Activity-regulated cytoskeleton-associated protein is a plasticity protein that in humans is encoded by the ARC gene. The gene is believed to derive from a retrotransposon. The protein is found in the neurons of tetrapods and other animals where it can form virus-like capsids that transport RNA between neurons.
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