Protein found in humans
DOCK10 |
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Identifiers |
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Aliases | DOCK10, DRIP2, Nbla10300, ZIZ3, Dock10, dedicator of cytokinesis 10 |
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External IDs | OMIM: 611518; MGI: 2146320; HomoloGene: 45952; GeneCards: DOCK10; OMA:DOCK10 - orthologs |
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Gene location (Human) |
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| Chr. | Chromosome 2 (human)[1] |
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| Band | 2q36.2 | Start | 224,765,090 bp[1] |
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End | 225,042,468 bp[1] |
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Gene location (Mouse) |
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| Chr. | Chromosome 1 (mouse)[2] |
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| Band | 1|1 C5 | Start | 80,478,790 bp[2] |
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End | 80,736,244 bp[2] |
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RNA expression pattern |
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Bgee | Human | Mouse (ortholog) |
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Top expressed in | - corpus callosum
- internal globus pallidus
- C1 segment
- buccal mucosa cell
- inferior ganglion of vagus nerve
- spleen
- granulocyte
- substantia nigra
- bone marrow cells
- subthalamic nucleus
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| Top expressed in | - mesenteric lymph nodes
- otolith organ
- utricle
- lateral septal nucleus
- spleen
- globus pallidus
- sciatic nerve
- stroma of bone marrow
- substantia nigra
- suprachiasmatic nucleus
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| More reference expression data |
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BioGPS |
| More reference expression data |
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Gene ontology |
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Molecular function | - protein binding
- guanyl-nucleotide exchange factor activity
- molecular function
| Cellular component | - extracellular exosome
- membrane
- nucleus
- cytoplasm
- cell projection
- dendritic spine
- nucleoplasm
- cytosol
- intracellular anatomical structure
| Biological process | - small GTPase mediated signal transduction
- regulation of cell migration
- B cell homeostasis
- marginal zone B cell differentiation
- positive regulation of GTPase activity
- dendritic spine morphogenesis
| Sources:Amigo / QuickGO |
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Orthologs |
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Species | Human | Mouse |
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Entrez | | |
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Ensembl | | |
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UniProt | | |
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RefSeq (mRNA) | |
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NM_001290263 NM_014689 NM_017718 NM_001363762 |
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RefSeq (protein) | |
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NP_001277192 NP_055504 NP_001350691 |
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NP_001272856 NP_780500 NP_001393483 NP_001393484 |
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Location (UCSC) | Chr 2: 224.77 – 225.04 Mb | Chr 1: 80.48 – 80.74 Mb |
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PubMed search | [3] | [4] |
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Wikidata |
View/Edit Human | View/Edit Mouse |
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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.[5] 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.[6] Dock10 is expressed in peripheral blood leukocytes[7] as well as in the brain, spleen, lung and thymus.[8]
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.[8] 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 contains an N-terminal PH domain, which, in Dock9/Zizimin1, mediates recruitment to the plasma membrane.[9] The DHR2 domain of Dock10 appears to bind to the small G proteins Cdc42, TC10 and TCL although these interactions are of low affinity.[8] The physiological role of Dock10 is poorly characterised, however a study in lymphocytes has shown that Dock10 expression is upregulated in B-lymphocytes and Chronic Lymphocytic Leukemia (CLL) cells in response to the cytokine IL-4.[7] This suggests that Dock10 may have a role in B-cell activation and proliferation. Another study in 2006 identified Dock10 as a protein that was overexpressed in some aggressive papillary thyroid carcinomas.[10]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000135905 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000038608 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Entrez Gene: DOCK10 dedicator of cytokinesis 10".
- ^ Côté JF, Vuori K (December 2002). "Identification of an evolutionarily conserved superfamily of DOCK180-related proteins with guanine nucleotide exchange activity". J. Cell Sci. 115 (Pt 24): 4901–13. doi:10.1242/jcs.00219. PMID 12432077.
- ^ a b Yelo E, Bernardo MV, Gimeno L, et al. (July 2008). "Dock10, a novel CZH protein selectively induced by interleukin-4 in human B lymphocytes". Mol. Immunol. 45 (12): 3411–18. doi:10.1016/j.molimm.2008.04.003. PMID 18499258.
- ^ a b c Nishikimi A, Meller N, Uekawa N, et al. (February 2005). "Zizimin2: a novel, DOCK180-related Cdc42 guanine nucleotide exchange factor expressed predominantly in lymphocytes". FEBS Letters. 579 (5): 1039–46. Bibcode:2005FEBSL.579.1039N. doi:10.1016/j.febslet.2005.01.006. PMID 15710388. S2CID 36721405.
- ^ Meller N, Westbrook MJ, Shannon JD, et al. (January 2008). "Function of the N-terminus of zizimin1: autoinhibition and membrane targeting". Biochem. J. 409 (2): 525–33. doi:10.1042/BJ20071263. PMC 2740492. PMID 17935486.
- ^ Fluge Ø, Bruland O, Akslen LA, et al. (February 2006). "Gene expression in poorly differentiated papillary thyroid carcinomas". Thyroid. 16 (2): 161–75. doi:10.1089/thy.2006.16.161. PMID 16676402.
Further reading
- Nishikimi A, Meller N, Uekawa N, et al. (2005). "Zizimin2: a novel, DOCK180-related Cdc42 guanine nucleotide exchange factor expressed predominantly in lymphocytes". FEBS Lett. 579 (5): 1039–46. Bibcode:2005FEBSL.579.1039N. doi:10.1016/j.febslet.2005.01.006. PMID 15710388. S2CID 36721405.
- Meller N, Merlot S, Guda C (2005). "CZH proteins: a new family of Rho-GEFs". J. Cell Sci. 118 (Pt 21): 4937–46. doi:10.1242/jcs.02671. PMID 16254241.
- Côté JF, Vuori K (2006). "In Vitro Guanine Nucleotide Exchange Activity of DHR-2/DOCKER/CZH2 Domains". Regulators and Effectors of Small GTPases: Rho Family. Methods in Enzymology. Vol. 406. pp. 41–57. doi:10.1016/S0076-6879(06)06004-6. ISBN 9780121828110. PMID 16472648.
External links
- Overview of all the structural information available in the PDB for UniProt: Q96BY6 (Dedicator of cytokinesis protein 10) at the PDBe-KB.