DOCK (protein)
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DOCK (protein)
DOCK (Dedicator of cytokinesis) is a family of related proteins involved in intracellular signalling networks. DOCK family members contain a RhoGEF domain to function as guanine nucleotide exchange factors to promote GDP release and GTP binding to specific Small GTPases of the Rho family (e.g., Rac and Cdc42), leading to their activation since Rho proteins are inactive when bound to GDP but active when bound to GTP. DOCK family proteins are categorised into four subfamilies based on their sequence homology: *DOCK-A subfamily **Dock180 (also known as Dock1) **Dock2 ** Dock5 *DOCK-B subfamily ** Dock3 (also known as MOCA and PBP) ** Dock4 *DOCK-C subfamily (also known as Zir subfamily) **Dock6 (also known as Zir1) ** Dock7 (also known as Zir2) ** Dock8 (also known as Zir3) *DOCK-D subfamily (also known as Zizimin subfamily) **Dock9 (also known as Zizimin1) ** Dock10 (also known as Zizimin3) **Dock11 Dock11 (Dedicator of cytokinesis), also known as Zizimin2, is a large (~240 kDa ...
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Proteins
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, responding to stimuli, providing structure to cells and organisms, and transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the nucleotide sequence of their genes, and which usually results in protein folding into a specific 3D structure that determines its activity. A linear chain of amino acid residues is called a polypeptide. A protein contains at least one long polypeptide. Short polypeptides, containing less than 20–30 residues, are rarely considered to be proteins and are commonly called peptides. The individual amino acid residues are bonded together by peptide bonds and adjacent amino acid residues. The sequence of amino acid residues ...
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Dock180
Dock180, (Dedicator of cytokinesis) also known as DOCK1, is a large (~180 kDa) protein involved in intracellular signalling networks. It is the mammalian ortholog of the ''C. elegans'' protein CED-5 and belongs to the DOCK family of Guanine nucleotide exchange factors (GEFs). Discovery Dock180 was identified, using a far-western blotting approach, as a binding partner of the adaptor protein Crk that was able to induce morphological changes in 3T3 fibroblasts. Subsequently it was reported that Dock180 was able to activate the small GTP-binding protein (G protein) Rac1 and this was later shown to happen via its ability to act as a GEF. Structure and function Dock180 is part of a large class of proteins (GEFs) which contribute to cellular signalling events by activating small G proteins. In their resting state G proteins are bound to Guanosine diphosphate (GDP) and their activation requires the dissociation of GDP and binding of guanosine triphosphate (GTP). GEFs activate G p ...
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Dock10
Dedicator of cytokinesis protein 10 (Dock10), also known as Zizimin3, is a large (~240 kDa) protein involved in intracellular signalling networks that in humans is encoded by the ''DOCK10'' gene. 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. Discovery Dock10 was identified via bioinformatic approaches as one of a family of evolutionarily conserved proteins (the DOCK family) that share significant sequence homology. Dock10 is expressed in peripheral blood leukocytes as well as in the brain, spleen, lung and thymus. 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 that 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 co ...
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Dock9
Dedicator of cytokinesis protein 9 (Dock9), also known as Zizimin1, is a large (~230 kDa) protein encoded in the human by the ''DOCK9'' gene, involved in intracellular signalling networks. It is a member of the DOCK-D subfamily of the DOCK family of guanine nucleotide exchange factors that function as activators of small G-proteins. Dock9 activates the small G protein Cdc42. Discovery Dock9 was discovered using an affinity proteomic approach designed to identify novel activators of the small G protein Cdc42 in fibroblasts. Subsequent northern blot analysis revealed that Dock9 is expressed primarily in the brain, heart, skeletal muscle, kidney, placenta and lung. Lower levels were detected in the colon, thymus, liver, small intestine and in leukocytes from peripheral blood. Structure and function Dock9 shares a similar structure of two core domains (known as DHR1 and DHR2), which are shared by all DOCK family members. The C-terminal DHR2 domain functions as an atypical ...
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Dock7
Dedicator of cytokinesis protein (Dock7) is a large (~240 kDa) protein encoded in the human by the ''DOCK7'' gene, involved in intracellular signalling networks. It is a member of the DOCK-C subfamily of the DOCK family of guanine nucleotide exchange factors (GEFs) which function as activators of small G-proteins. Dock7 activates isoforms of the small G protein Rac. Discovery Dock7 was identified as one of a number of proteins which share high sequence similarity with the previously described protein Dock180, the archetypal member of the DOCK family. Dock7 expression has been reported in neurons and in the HEK 293 cell line. Structure and function Dock7 is part of a large class of proteins (GEFs) which contribute to cellular signalling events by activating small G proteins. In their resting state G proteins are bound to Guanosine diphosphate (GDP) and their activation requires the dissociation of GDP and binding of guanosine triphosphate (GTP). GEFs activate G proteins b ...
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Dock6
Dock6 (Dedicator of cytokinesis 6), also known as Zir1 is a large (~200 kDa) protein involved in intracellular signalling networks. It is a member of the DOCK-C subfamily of the DOCK family of guanine nucleotide exchange factors which function as activators of small G proteins. Discovery Dock6 was identified as one of a family of proteins which share high sequence similarity with Dock180, the archetypal member of the DOCK family. It has a similar domain arrangement to other DOCK proteins, with a DHR1 domain known in other proteins to bind phospholipids, and a DHR2 domain containing the GEF activity. Function There is currently very little information about the cellular role of this protein. However, Dock6 has been reported to exhibit dual GEF specificity towards the small G proteins Rac1 and Cdc42. It is the only DOCK family member reported to activate both of these G proteins. The same study also showed that transfection of the Dock6 DHR2 domain into N1E-115 neuroblastoma c ...
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Dock4
Dock4, (Dedicator of cytokinesis 4) also known as DOCK4, is a large (~190 kDa) protein involved in intracellular signalling networks. It is a member of the DOCK-B subfamily of the DOCK family of guanine nucleotide exchange factors (GEFs) which function as activators of small G proteins. Dock4 activates the small G proteins Rac and Rap1. Discovery Dock4 was discovered as a gene product which was disrupted during tumour progression in a murine cancer model-derived osteosarcoma cell line. Subsequent Northern blot analysis revealed high levels of Dock4 expression in skeletal muscle, prostate and ovary as well as lower levels in the heart, placenta and colon. A separate study has reported expression of a Dock4 splice variant ( Dock4-Ex49) in the brain, inner ear and eye. Structure and function Dock4 is part of a large class of proteins (GEFs) which contribute to cellular signalling events by activating small G proteins. In their resting state G proteins are bound to Gu ...
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Dock3
Dock3 (Dedicator of cytokinesis 3), also known as MOCA (modifier of cell adhesion) and PBP (presenilin-binding protein), is a large (~180 kDa) protein involved in intracellular signalling networks. It is a member of the DOCK-B subfamily of the DOCK family of guanine nucleotide exchange factors (GEFs) which function as activators of small G proteins. Dock3 specifically activates the small G protein Rac. Discovery Dock3 was originally discovered in a screen for proteins that bind presenilin (a transmembrane protein which is mutated in early onset Alzheimer's disease). Dock3 is specifically expressed in neurones (primarily in the cerebral cortex and hippocampus). Structure and function Dock3 is part of a large class of proteins (GEFs) which contribute to cellular signalling events by activating small G proteins. In their resting state G proteins are bound to Guanosine diphosphate (GDP) and their activation requires the dissociation of GDP and binding of guanosine triphospha ...
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Dock5
Dock5 (Dedicator of cytokinesis 5), also known as DOCK5, is a large (~180 kDa) protein involved in intracellular signalling networks. It is a member of the DOCK-A subfamily of the DOCK family of guanine nucleotide exchange factors (GEFs) which function as activators of small G proteins. Dock5 is predicted to activate the small G protein Rac. Function Dock5 shares significant sequence identity with Dock180, the archetypal member of the DOCK family. It is therefore predicted to partake in similar interactions although this has yet to be demonstrated. Indeed, the function and signalling properties of Dock5 are poorly understood thus far. Dock5 has been identified as a crucial signalling protein in osteoclasts An osteoclast () is a type of bone cell that breaks down bone tissue. This function is critical in the maintenance, repair, and remodeling of bones of the vertebral skeleton. The osteoclast disassembles and digests the composite of hydrated prote ..., and suppression of ...
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Dock2
Dock2 (Dedicator of cytokinesis 2), also known as DOCK2, is a large (~180 kDa) protein involved in intracellular Cell signalling, signalling networks. It is a member of the DOCK-A subfamily of the DOCK (protein), DOCK family of guanine nucleotide exchange factors (GEFs) which function as activators of small G proteins. Dock2 specifically activates isoforms of the small G protein Rac (GTPase), Rac. Discovery Dock2 was first characterised as one of a number of proteins which shared high sequence similarity with the previously described protein Dock180, the archetypal member of the DOCK family. Whereas Dock180 gene expression, expression is near ubiquitous in mammals, Dock2 appears to be expressed specifically in leukocytes and is considered to be the principal DOCK family member in these cells. Structure and function Dock2 is part of a large class of proteins (GEFs) which contribute to cellular signalling events by activating small G proteins. In their resting state G proteins are b ...
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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 speciation event (orthologs), or a duplication event (paralogs), or else a horizontal (or lateral) gene transfer event (xenologs). Homology among DNA, RNA, or proteins is typically inferred from their nucleotide or amino acid sequence similarity. Significant similarity is strong evidence that two sequences are related by evolutionary changes from a common ancestral sequence. Alignments of multiple sequences are used to indicate which regions of each sequence are homologous. Identity, similarity, and conservation The term "percent homology" is often used to mean "sequence similarity”, that is the percentage of identical residues (''percent identity''), or the percentage of residues conserved with similar physicochemical properties (' ...
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