DOC2B | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Aliases | DOC2B , DOC2BL, double C2 domain beta | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM: 604568; MGI: 1100497; HomoloGene: 20796; GeneCards: DOC2B; OMA:DOC2B - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Double C2-like domain-containing protein beta is a protein that in humans is encoded by the DOC2B gene. [5] [6]
There are at least two protein isoforms of the Double C2 protein, namely alpha (DOC2A) and beta (DOC2B), which contain two C2-like domains. DOC2A and DOC2B are encoded by different genes; these genes are at times confused with the unrelated DAB2 gene which was initially named DOC-2. Doc2b enhances Ca(2+)-dependent exocytosis in adipocytes, [7] chromaffin cells of the adrenal gland [8] and beta cells in the pancreas. [9] In the central nervous system, Doc2b contributes to the spontaneous release of neurotransmitters, which was thought to be acting as a high-affinity Ca(2+) sensor for exocytosis of synaptic vesicles [10] However, further work has shown that while DOC2b is both important for spontaneous exocytosis of synaptic vesicles and binds Calcium, it does not in fact change the calcium dependence of spontaneous synaptic vesicle release and thus can not be the calcium sensor for this process. [11]
Exocytosis is a form of active transport and bulk transport in which a cell transports molecules out of the cell. As an active transport mechanism, exocytosis requires the use of energy to transport material. Exocytosis and its counterpart, endocytosis, are used by all cells because most chemical substances important to them are large polar molecules that cannot pass through the hydrophobic portion of the cell membrane by passive means. Exocytosis is the process by which a large amount of molecules are released; thus it is a form of bulk transport. Exocytosis occurs via secretory portals at the cell plasma membrane called porosomes. Porosomes are permanent cup-shaped lipoprotein structures at the cell plasma membrane, where secretory vesicles transiently dock and fuse to release intra-vesicular contents from the cell.
In a neuron, synaptic vesicles store various neurotransmitters that are released at the synapse. The release is regulated by a voltage-dependent calcium channel. Vesicles are essential for propagating nerve impulses between neurons and are constantly recreated by the cell. The area in the axon that holds groups of vesicles is an axon terminal or "terminal bouton". Up to 130 vesicles can be released per bouton over a ten-minute period of stimulation at 0.2 Hz. In the visual cortex of the human brain, synaptic vesicles have an average diameter of 39.5 nanometers (nm) with a standard deviation of 5.1 nm.
Phosphatidylinositol 4,5-bisphosphate or PtdIns(4,5)P2, also known simply as PIP2 or PI(4,5)P2, is a minor phospholipid component of cell membranes. PtdIns(4,5)P2 is enriched at the plasma membrane where it is a substrate for a number of important signaling proteins. PIP2 also forms lipid clusters that sort proteins.
Synaptosomal-Associated Protein, 25kDa (SNAP-25) is a Target Soluble NSF (N-ethylmaleimide-sensitive factor) Attachment Protein Receptor (t-SNARE) protein encoded by the SNAP25 gene found on chromosome 20p12.2 in humans. SNAP-25 is a component of the trans-SNARE complex, which accounts for membrane fusion specificity and directly executes fusion by forming a tight complex that brings the synaptic vesicle and plasma membranes together.
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.
Complexin (also known as synaphin) refers to a one of a small set of eukaryotic cytoplasmic neuronal proteins which binds to the SNARE protein complex (SNAREpin) with a high affinity. These are called synaphin 1 and 2. In the presence of Ca2+, the transport vesicle protein synaptotagmin displaces complexin, allowing the SNARE protein complex to bind the transport vesicle to the presynaptic membrane.
Syntaxin-1A is a protein that in humans is encoded by the STX1A gene.
Ras-related protein Rab-3A is a protein that in humans is encoded by the RAB3A gene. It is involved in calcium-triggered exocytosis in neurons.
Synaptotagmin-1 is a protein that in humans is encoded by the SYT1 gene.
Amyloid beta A4 precursor protein-binding family A member 1 is a protein that in humans is encoded by the APBA1 gene.
Neurexin-1-alpha is a protein that in humans is encoded by the NRXN1 gene.
Amyloid beta A4 precursor protein-binding family A member 2 is a protein that in humans is encoded by the APBA2 gene.
Regulating synaptic membrane exocytosis protein 1 is a protein that in humans is encoded by the RIMS1 gene.
Rabphilin-3A is a protein that in humans is encoded by the RPH3A gene. It contains two C2 domains and binds calcium ions at low micromolar concentration. Rabphilin was shown to regulate neurotransmitter release in hippocampal neurons after neurons had an increased synaptic activity and their release rate was depressed.
Protein unc-13 homolog B is a protein that in humans is encoded by the UNC13B gene.
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.
Spectrin beta chain, brain 2 is a protein that in humans is encoded by the SPTBN2 gene.
Double C2-like domain-containing protein alpha is a protein that in humans is encoded by the DOC2A gene.
Axon terminals are distal terminations of the branches of an axon. An axon, also called a nerve fiber, is a long, slender projection of a nerve cell that conducts electrical impulses called action potentials away from the neuron's cell body to transmit those impulses to other neurons, muscle cells, or glands. Most presynaptic terminals in the central nervous system are formed along the axons, not at their ends.
The ribbon synapse is a type of neuronal synapse characterized by the presence of an electron-dense structure, the synaptic ribbon, that holds vesicles close to the active zone. It is characterized by a tight vesicle-calcium channel coupling that promotes rapid neurotransmitter release and sustained signal transmission. Ribbon synapses undergo a cycle of exocytosis and endocytosis in response to graded changes of membrane potential. It has been proposed that most ribbon synapses undergo a special type of exocytosis based on coordinated multivesicular release. This interpretation has recently been questioned at the inner hair cell ribbon synapse, where it has been instead proposed that exocytosis is described by uniquantal release shaped by a flickering vesicle fusion pore.