DOC2B

Last updated
DOC2B
Identifiers
Aliases DOC2B , DOC2BL, double C2 domain beta
External IDs OMIM: 604568; MGI: 1100497; HomoloGene: 20796; GeneCards: DOC2B; OMA:DOC2B - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_003585

NM_007873

RefSeq (protein)

NP_003576

NP_031899

Location (UCSC) Chr 17: 0.14 – 0.18 Mb Chr 11: 75.66 – 75.69 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Double C2-like domain-containing protein beta is a protein that in humans is encoded by the DOC2B gene. [5] [6]

Contents

Function

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]

Related Research Articles

<span class="mw-page-title-main">Exocytosis</span> Active transport and bulk transport in which a cell transports molecules out of the cell

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.

<span class="mw-page-title-main">Synaptic vesicle</span> Neurotransmitters that are released at the synapse

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.

<span class="mw-page-title-main">Phosphatidylinositol 4,5-bisphosphate</span> Chemical compound

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.

<span class="mw-page-title-main">SNAP25</span> Protein-coding gene in the species Homo sapiens

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.

<span class="mw-page-title-main">Synaptotagmin</span>

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.

<span class="mw-page-title-main">Complexin</span>

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.

<span class="mw-page-title-main">STX1A</span> Protein-coding gene in the species Homo sapiens

Syntaxin-1A is a protein that in humans is encoded by the STX1A gene.

<span class="mw-page-title-main">RAB3A</span> Protein-coding gene in the species Homo sapiens

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.

<span class="mw-page-title-main">SYT1</span> Protein-coding gene in the species Homo sapiens

Synaptotagmin-1 is a protein that in humans is encoded by the SYT1 gene.

<span class="mw-page-title-main">APBA1</span> Protein-coding gene in the species Homo sapiens

Amyloid beta A4 precursor protein-binding family A member 1 is a protein that in humans is encoded by the APBA1 gene.

<span class="mw-page-title-main">NRXN1</span> Protein-coding gene in the species Homo sapiens

Neurexin-1-alpha is a protein that in humans is encoded by the NRXN1 gene.

<span class="mw-page-title-main">APBA2</span> Protein-coding gene in the species Homo sapiens

Amyloid beta A4 precursor protein-binding family A member 2 is a protein that in humans is encoded by the APBA2 gene.

<span class="mw-page-title-main">RIMS1</span> Gene of the species Homo sapiens

Regulating synaptic membrane exocytosis protein 1 is a protein that in humans is encoded by the RIMS1 gene.

<span class="mw-page-title-main">RPH3A</span> Gene of the species Homo sapiens

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.

<span class="mw-page-title-main">UNC13B</span> Protein-coding gene in the species Homo sapiens

Protein unc-13 homolog B is a protein that in humans is encoded by the UNC13B gene.

<span class="mw-page-title-main">DNAJC5</span> Protein-coding gene in the species Homo sapiens

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.

<span class="mw-page-title-main">SPTBN2</span> Protein-coding gene in the species Homo sapiens

Spectrin beta chain, brain 2 is a protein that in humans is encoded by the SPTBN2 gene.

<span class="mw-page-title-main">DOC2A</span> Protein-coding gene in the species Homo sapiens

Double C2-like domain-containing protein alpha is a protein that in humans is encoded by the DOC2A gene.

<span class="mw-page-title-main">Axon terminal</span> Nerve fiber part

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.

References

  1. 1 2 3 ENSG00000272636 GRCh38: Ensembl release 89: ENSG00000272670, ENSG00000272636 Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000020848 Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Orita S, Sasaki T, Naito A, Komuro R, Ohtsuka T, Maeda M, Suzuki H, Igarashi H, Takai Y (Feb 1995). "Doc2: a novel brain protein having two repeated C2-like domains". Biochem Biophys Res Commun. 206 (2): 439–48. doi:10.1006/bbrc.1995.1062. PMID   7826360.
  6. "Entrez Gene: DOC2B double C2-like domains, beta".
  7. Fukuda N, Emoto M, Nakamori Y, Taguchi A, Miyamoto S, Uraki S, Oka Y, Tanizawa Y (Feb 2009). "DOC2B: a novel syntaxin-4 binding protein mediating insulin-regulated GLUT4 vesicle fusion in adipocytes". Diabetes. 58 (2): 377–84. doi:10.2337/db08-0303. PMC   2628611 . PMID   19033398.
  8. Friedrich R, Groffen AJ, Connell E, van Weering JR, Gutman O, Henis YI, Davletov B, Ashery U (Jul 2008). "DOC2B acts as a calcium switch and enhances vesicle fusion". J Neurosci. 28 (27): 6794–806. doi:10.1523/JNEUROSCI.0538-08.2008. PMC   2673511 . PMID   18596155.
  9. Miyazaki M, Emoto M, Fukuda N, Hatanaka M, Taguchi A, Miyamoto S, Tanizawa Y (Jul 2009). "DOC2b is a SNARE regulator of glucose-stimulated delayed insulin secretion". Biochem Biophys Res Commun. 384 (4): 461–5. doi:10.1016/j.bbrc.2009.04.133. PMID   19410553.
  10. Groffen AJ, Martens S, Díez Arazola R, Cornelisse LN, Lozovaya N, de Jong AP, Goriounova NA, Habets RL, Takai Y, Borst JG, Brose N, McMahon HT, Verhage M (Mar 2010). "Doc2b is a high-affinity Ca2+ sensor for spontaneous neurotransmitter release". Science. 327 (5973): 1614–8. doi:10.1126/science.1183765. PMC   2846320 . PMID   20150444.

Further reading