Dock11

Dedicator of cytokinesis 11
Identifiers
Symbols	DOCK11; ACG; FLJ32122; FLJ43653; ZIZ2; bB128O4.1
External IDs	OMIM: 300681 MGI: 1923224 HomoloGene: 70950 GeneCards: DOCK11 Gene
Gene Ontology Molecular function • guanyl-nucleotide exchange factor activity • Rho guanyl-nucleotide exchange factor activity • GTP binding • Rho GTPase binding • GTPase binding Cellular component • cytosol Biological process • blood coagulation Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	139818	75974
Ensembl	ENSG00000147251	ENSMUSG00000031093
UniProt	Q5JSL3	A2AF47
RefSeq (mRNA)	NM_144658	NM_001009947.3
RefSeq (protein)	NP_653259	NP_001009947.2
Location (UCSC)	Chr X: 117.63 – 117.82 Mb	Chr X: 33.43 – 33.62 Mb
PubMed search	[1]	[2]

Dock11 (Dedicator of cytokinesis), also known as Zizimin2, is a large (~240 kDa) protein involved in intracellular signalling networks.^[1][2] 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.

Discovery

Dock11 was identified as a protein which is highly expressed in Germinal center B lymphocytes.^[3] Subsequent RT-PCR analysis revealed expression of this protein in the spleen, thymus, bone marrow and in peripheral blood lymphocytes. Dock11 is expressed at lower levels in NIH-3T3 fibroblasts, C2C12 myoblasts and Neuro-2A neuroblastoma cells. Dock11 mRNA has also been detected in the pars intermedia.^[4]

Structure and Function

Dock11 exhibits the same domain arrangement as other memebrs of the DOCK-D/Zizimin subfamily and shares the highest level of sequence identity with Dock9.^[3] It contains a DHR2 domain which mediates GEF activity and a DHR1 domain domain which may interact with membrane phospholipids. It also contains an N-terminal PH domain which may be involved in its recruitment to the plasma membrane. Dock11 binds and activates nucleotide-free Cdc42 via its DHR2 domain^[3] and has also been reported to mediate positive feedback on active, GTP-bound Cdc42,^[5] although this interaction required a small N-terminal region of Dock11 in addition to the DHR2 domain. Cdc42 in turn regulates signaling pathways that control diverse cellular functions including morphology, migration, endocytosis and cell cycle progression.^[6] Gene expression studies have suggested that Dock11 may have a role in the development of pituitary and testicular tumours.^[4][7]

References

1. ^ "Entrez Gene: DOCK11 dedicator of cytokinesis 11". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=139818. 
2. ^ 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. 
3. ^ ^{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. doi:10.1016/j.febslet.2005.01.006. PMID 15710388. 
4. ^ ^{a b} Chien WM, Garrison K, Caufield E et al. (March 2007). "Differential gene expression of p27Kip1 and Rb knockokut pituitary tumors associated with altered growth and angiogenesis". Cell Cycle 6 (6): 750–57. doi:10.4161/cc.6.6.3986. PMC 2040307. PMID 17361101. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2040307. 
5. ^ Lin Q, Yang W, Baird D et al. (November 2006). "Identification of a DOCK180-related guanine nucleotide exchange factor that is capable of mediating a positive feedback activation of Cdc42". J. Biol. Chem. 281 (46): 35253–62. doi:10.1074/jbc.M606248200. PMID 16968698. 
6. ^ Sinha S, Yang W (May 2008). "Cellular signaling for activation of Rho GTPase Cdc42". Cell. Signal. article in press (11): 1927–34. doi:10.1016/j.cellsig.2008.05.002. PMID 18558478. 
7. ^ Almstrup K, Leffers H, Lothe RA et al. (August 2007). "Improved gene expression signature of testicular carcinoma in situ". Int. J. Androl. 30 (4): 292–302. doi:10.1111/j.1365-2605.2007.00758.x. PMID 17488342. 

Further reading

• Côté JF, Vuori K (2007). "GEF what? Dock180 and related proteins help Rac to polarize cells in new ways". Trends Cell Biol. 17 (8): 383–93. doi:10.1016/j.tcb.2007.05.001. PMC 2887429. PMID 17765544. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2887429. 
• Côté JF, Vuori K (2006). "In vitro guanine nucleotide exchange activity of DHR-2/DOCKER/CZH2 domains". Methods Enzymol. 406: 41–57. doi:10.1016/S0076-6879(06)06004-6. PMID 16472648. 
• 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. 
• Yelo E, Bernardo MV, Gimeno L et al. (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.