Dock11

DOCK11
Identifiers
Aliases DOCK11, ACG, ZIZ2, bB128O4.1, Dock11, dedicator of cytokinesis 11
External IDs MGI: 1923224 HomoloGene: 70950 GeneCards: DOCK11
Orthologs
Species Human Mouse
Entrez

139818

75974

Ensembl

ENSG00000147251

ENSMUSG00000031093

UniProt

Q5JSL3

A2AF47

RefSeq (mRNA)

NM_144658

NM_001009947
NM_177745

RefSeq (protein)

NP_653259.3

NP_001009947.2

Location (UCSC) Chr X: 118.5 – 118.69 Mb Chr X: 35.89 – 36.08 Mb
PubMed search [1] [2]
Wikidata
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Dock11 (Dedicator of cytokinesis), also known as Zizimin2, is a large (~240 kDa) protein involved in intracellular signalling networks.[3][4] 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.[5] 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.[6]

Structure and Function

Dock11 exhibits the same domain arrangement as other members of the DOCK-D/Zizimin subfamily and shares the highest level of sequence identity with Dock9.[5] It contains a DHR2 domain which mediates GEF activity and a DHR1 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[5] and has also been reported to mediate positive feedback on active, GTP-bound Cdc42,[7] 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.[8] Gene expression studies have suggested that Dock11 may have a role in the development of pituitary and testicular tumours.[6][9]

References

  1. ↑ "Human PubMed Reference:".
  2. ↑ "Mouse PubMed Reference:".
  3. ↑ "Entrez Gene: DOCK11 dedicator of cytokinesis 11".
  4. ↑ 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.
  5. 1 2 3 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.
  6. 1 2 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 2040307Freely accessible. PMID 17361101.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 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


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