Dedicator of cytokinesis protein 10 (Dock10), also known as Zizimin3, is a large (~240 kDa)
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
involved in
intracellular signalling networks that in humans is encoded by the ''DOCK10''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
.
It is a member of the DOCK-D subfamily of the
DOCK
A dock (from Dutch language, Dutch ''dok'') is the area of water between or next to one or a group of human-made structures that are involved in the handling of boats or ships (usually on or near a shore) or such structures themselves. The ex ...
family of
guanine nucleotide exchange factor
Guanine nucleotide exchange factors (GEFs) are proteins or protein domains that activate monomeric GTPases by stimulating the release of guanosine diphosphate (GDP) to allow binding of guanosine triphosphate (GTP). A variety of unrelated structu ...
s, which function as activators of
small G-proteins.
Discovery
Dock10 was identified via
bioinformatic approaches as one of a family of
evolutionarily conserved
In evolutionary biology, conserved sequences are identical or similar sequences in nucleic acids ( DNA and RNA) or proteins across species ( orthologous sequences), or within a genome ( paralogous sequences), or between donor and receptor tax ...
proteins (the DOCK family) that share significant
sequence homology
Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a spe ...
.
Dock10 is expressed in
peripheral blood
Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the c ...
leukocyte
White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...
s
as well as in the
brain
A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...
,
spleen
The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes . ,
lung
The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of t ...
and
thymus
The thymus is a specialized primary lymphoid organ of the immune system. Within the thymus, thymus cell lymphocytes or ''T cells'' mature. T cells are critical to the adaptive immune system, where the body adapts to specific foreign invaders. ...
.
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 domain
DHR2 (DOCK homology region 2), 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 (GEF) domain for ...
that is involved in G protein binding and a
DHR1 domain
DHR1 (DOCK homology region 1), 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 ...
, which, in some DOCK family proteins, interacts with membrane
phospholipids
Phospholipids, are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typ ...
. Like other DOCK-D subfamily proteins Dock10 contains an
N-terminal
The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...
PH domain
In chemistry, pH (), historically denoting "potential of hydrogen" (or "power of hydrogen"), is a scale used to specify the acidity or basicity of an aqueous solution. Acidic solutions (solutions with higher concentrations of ions) are mea ...
, which, in
Dock9/Zizimin1, mediates recruitment to the
plasma membrane
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (t ...
.
The DHR2 domain of Dock10 appears to bind to the small G proteins
Cdc42,
TC10 and
TCL
TCL or Tcl or TCLs may refer to:
Business
* TCL Technology, a Chinese consumer electronics and appliance company
**TCL Electronics, a subsidiary of TCL Technology
* Texas Collegiate League, a collegiate baseball league
* Trade Centre Limited, a ...
although these interactions are of low affinity.
The physiological role of Dock10 is poorly characterised, however a study in
lymphocyte
A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic ad ...
s has shown that Dock10
expression is upregulated in
B-lymphocytes and
Chronic Lymphocytic Leukemia
Chronic lymphocytic leukemia (CLL) is a type of cancer in which the bone marrow makes too many lymphocytes (a type of white blood cell). Early on, there are typically no symptoms. Later, non-painful lymph node swelling, feeling tired, fever, nigh ...
(CLL) cells in response to the
cytokine
Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...
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.
References
Further reading
*
*
*
External links
*
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