| DOCK9 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Aliases | DOCK9 , ZIZ1, ZIZIMIN1, Dock9, dedicator of cytokinesis 9 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 607325 MGI: 106321 HomoloGene: 41026 GeneCards: DOCK9 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Dock9 (Dedicator of cytokinesis 9), also known as Zizimin1, is a large (~230 kDa) protein involved in intracellular signalling networks. [5] 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.
Dock9 was discovered using an affinity proteomic approach designed to identify novel activators of the small G protein Cdc42 in fibroblasts. [6] 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.
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 GEF domain for small G proteins (see Dock180: structure and function) and the DHR1 domain is known, in some DOCK-A/B/C subfamily proteins, to be involved in their recruitment to the plasma membrane. Unlike DOCK-A/B/C proteins DOCK-D proteins (including Dock9) contain an N-terminal pleckstrin homology (PH) domain that mediates their recruitment to the membrane. [7] Dock9, along with other DOCK-C/D subfamily members, can activate Cdc42 in vitro and in vivo via its DHR2 domain. [6] However, Dock9 adopts an autoinhibitory conformation that masks the DHR2 domain in its resting state. [7] The mechanism by which this autoinhibition is overcome is still unclear although in some other DOCK proteins, which also undergo autoinhibition, it requires an interaction with adaptor proteins such as ELMO. [8] [9] Dock9 has also been reported to dimerise, under resting conditions, via its DHR2 domains and this study suggests that other DOCK family proteins may also behave in the same way. [10] Recent analysis of a chromosomal region associated with susceptibility to bipolar disorder revealed that single nucleotide polymorphisms in the DOCK9 gene contribute to the risk and severity of this condition. [11]
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 structural domains have been shown to exhibit guanine nucleotide exchange activity. Some GEFs can activate multiple GTPases while others are specific to a single GTPase.
RhoGEF domain describes two distinct structural domains with guanine nucleotide exchange factor (GEF) activity to regulate small GTPases in the Rho family. Rho small GTPases are inactive when bound to GDP but active when bound to GTP; RhoGEF domains in proteins are able to promote GDP release and GTP binding to activate specific Rho family members, including RhoA, Rac1 and Cdc42.
Rho guanine nucleotide exchange factor 6 is a protein that, in humans, is encoded by the ARHGEF6 gene.
Dock180, also known as DOCK1, is a large 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).
RhoG is a small monomeric GTP-binding protein, and is an important component of many intracellular signalling pathways. It is a member of the Rac subfamily of the Rho family of small G proteins and is encoded by the gene RHOG.
Dock2, also known as DOCK2, is a large 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. Dock2 specifically activates isoforms of the small G protein Rac.
Rap guanine nucleotide exchange factor 2 is a protein that in humans is encoded by the RAPGEF2 gene.
Dock7, also known as Zir2, is a large protein 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.
Dedicator of cytokinesis protein 10 (Dock10), also known as Zizimin3, is a large 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.
Dock4, also known as DOCK4, is a large 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.
Ras-specific guanine nucleotide-releasing factor 2 is a protein that in humans is encoded by the RASGRF2 gene.
DOCK8, also known as Zir3, is a large protein 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.
Dock3, also known as MOCA and PBP, is a large 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.
Rho guanine nucleotide exchange factor 9 is a protein that in humans is encoded by the ARHGEF9 gene.
GTPase activating protein and VPS9 domains 1, also known as GAPVD1, Gapex-5 and RME-6 is a protein which in humans is encoded by the GAPVD1 gene.
DOCK 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, leading to their activation since Rho proteins are inactive when bound to GDP but active when bound to GTP.
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 protein–protein interactions.
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 (GEF) domain for small G proteins of the Rho family. DHR2 domains bear no significant similarity to the well described DH domain present in other RhoGEFs such as Vav, P-Rex and TRIO. Indeed, the most divergent mammalian DHR2 domains share only 16-17% sequence similarity.
Dock6, also known as Zir1 is a large 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.
Dock11, also known as Zizimin2, 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 (GEFs) which function as activators of small G proteins. Dock11 activates the small G protein Cdc42.
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