DOCK10
Encyclopedia
Dock10 also known as Zizimin3, is a large (~240 kDa) protein
involved in intracellular
signalling networks. It is a member of the DOCK-D subfamily of the DOCK
family of guanine nucleotide exchange factor
s which function as activators of small G protein
s.
leukocytes as well as in the brain
, spleen
, lung
and thymus
.
which is involved in G protein binding and a DHR1 domain
which, in some DOCK family proteins, interacts with membrane phospholipids. Like other DOCK-D subfamily proteins Dock10 contains an N-terminal PH domain which, in Dock9/Zizimin1
, mediates recruitment to the plasma membrane. The DHR2 domain of Dock10 appears to bind to the small G proteins Cdc42
, TC10
and TCL
although these interactions are of low affinity. The physiological role of Dock10 is poorly characterised, however a study in lymphocyte
s has shown that Dock10 expression
is upregulated in B-lymphocytes and Chronic Lymphocytic Leukemia
(CLL) cells in response to the cytokine
IL-4. This suggests that Dock10 may have a role in B-cell activation and proliferation. Another study identified Dock10 as a protein that was overexpressed in some aggressive papillary thyroid carcinomas.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
involved in intracellular
Intracellular
Not to be confused with intercellular, meaning "between cells".In cell biology, molecular biology and related fields, the word intracellular means "inside the cell".It is used in contrast to extracellular...
signalling networks. It is a member of the DOCK-D subfamily of the DOCK
DOCK (protein)
DOCK is a family of related proteins involved in intracellular signalling networks. Studies to date suggest that this family act as guanine nucleotide exchange factors for small G proteins of the Rho family, such as Rac and Cdc42...
family of guanine nucleotide exchange factor
Guanine nucleotide exchange factor
Guanine nucleotide exchange factors activate monomeric GTPases by stimulating the release of guanosine diphosphate to allow binding of guanosine triphosphate . A variety of unrelated structural domains have been shown to exhibit guanine nucleotide exchange activity...
s which function as activators of small G protein
G protein
G proteins are a family of proteins involved in transmitting chemical signals outside the cell, and causing changes inside the cell. They communicate signals from many hormones, neurotransmitters, and other signaling factors. G protein-coupled receptors are transmembrane receptors...
s.
Discovery
Dock10 was identified via bioinformatic approaches as one of a family of evolutionarily conserved proteins (the DOCK family) which share significant sequence homology. Dock10 is expressed in peripheral bloodPeripheral blood cell
Peripheral blood cells are the cellular components of blood, consisting of red blood cells, white blood cells, and platelets, which are found within the circulating pool of blood and not sequestered within the lymphatic system, spleen, liver, or bone marrow....
leukocytes as well as in the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
, spleen
Spleen
The spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system. In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock...
, lung
Lung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...
and thymus
Thymus
The thymus is a specialized organ of the immune system. The thymus produces and "educates" T-lymphocytes , which are critical cells of the adaptive immune system....
.
Structure and Function
Dock10 shares the same domain arrangement as other members of the DOCK-D/Zizimin subfamily as well as a high level of sequence similarity. It contains a DHR2 domainDHR2 domain
DHR2 , also known as CZH2 or Docker2, is a protein domain of approximately 450-550 amino acids that is present in the DOCK family of proteins. This domain functions as a guanine nucleotide exchange factor domain for small G proteins of the Rho family...
which is involved in G protein binding and a DHR1 domain
DHR1 domain
DHR1 , also known as CZH1 or Docker1, is a protein domain of approximately 200-250 amino acids that is present in the DOCK family of signalling proteins. This domain binds phospholipids and so may assist in recruitment to cellular membranes. There is evidence that this domain may also mediate...
which, in some DOCK family proteins, interacts with membrane phospholipids. Like other DOCK-D subfamily proteins Dock10 contains an N-terminal PH domain which, in Dock9/Zizimin1
DOCK9
Dock9 , also known as Zizimin1, is a large protein involved in intracellular signalling networks. It is a member of the DOCK-D subfamily of the DOCK family of guanine nucleotide exchange factors which function as activators of small G proteins...
, mediates recruitment to the plasma membrane. The DHR2 domain of Dock10 appears to bind to the small G proteins Cdc42
CDC42
Cell division control protein 42 homolog also known as CDC42 is a protein involved in regulation of the cell cycle. In humans, CDC42 is encoded by the CDC42 gene.- Function :...
, TC10
TC10 protein
TC10 is a small signaling G protein , and is a member of the Rho family of GTPases.Further reading: Rho family of GTPases...
and TCL
TCL (GTPase)
TCL is a small signaling G protein , and is a member of the Rho family of GTPases.,.TCL shares 85% and 78% amino acid similarity to TC10 and Cdc42, respectively. TCL mRNA is 2.5 kb long and is mainly expressed in heart. In vitro, TCL shows rapid GDP/GTP exchange and displays higher GTP...
although these interactions are of low affinity. The physiological role of Dock10 is poorly characterised, however a study in lymphocyte
Lymphocyte
A lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
s has shown that Dock10 expression
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
is upregulated in B-lymphocytes and Chronic Lymphocytic Leukemia
Chronic lymphocytic leukemia
B-cell chronic lymphocytic leukemia , also known as chronic lymphoid leukemia , is the most common type of leukemia. Leukemias are cancers of the white blood cells . CLL affects B cell lymphocytes. B cells originate in the bone marrow, develop in the lymph nodes, and normally fight infection by...
(CLL) cells in response to the cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
IL-4. This suggests that Dock10 may have a role in B-cell activation and proliferation. Another study identified Dock10 as a protein that was overexpressed in some aggressive papillary thyroid carcinomas.