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Gene Review

DOCK4  -  dedicator of cytokinesis 4

Homo sapiens

Synonyms: Dedicator of cytokinesis protein 4, FLJ34238, KIAA0716
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Disease relevance of DOCK4

  • Expression of wild-type, but not mutant, DOCK4 in mouse osteosarcoma cells with a deletion of the endogenous gene suppresses growth in soft agar and tumor invasion in vivo [1].
  • DOCK4 mutations are present in a subset of human cancer cell lines; a recurrent missense mutant identified in human prostate and ovarian cancers encodes a protein that is defective in Rap1 activation [1].

High impact information on DOCK4


Biological context of DOCK4

  • Notably, a recently characterized tumor suppressor gene, DOCK4, and an evolutionarily conserved zinc finger gene, ZNF277, localize to this interval, head to head, within <0.5 kb of each other [4].
  • A new knowledge-based scoring function (PMF-score), implemented into the DOCK4 program, was used to screen a database of 3247 small molecules for binding to the FK506 binding protein (FKBP) [5].
  • On the other hand, RNA interference-mediated knockdown of Dock4 in NIH3T3 cells reduced cell migration [3].

Anatomical context of DOCK4

  • Detailed molecular analysis revealed that a novel DOCK4 isoform (DOCK4-Ex49) is expressed in the brain, eye and inner ear tissues [2].

Other interactions of DOCK4

  • DOCK4 with force field and PMF scoring as well as FlexX were used to evaluate the predictive power of these docking/scoring approaches to identify the correct binding mode of 61 MMP-3 inhibitors in a crystal structure of stromelysin and also to rank them according to their different binding affinities [6].


  1. DOCK4, a GTPase activator, is disrupted during tumorigenesis. Yajnik, V., Paulding, C., Sordella, R., McClatchey, A.I., Saito, M., Wahrer, D.C., Reynolds, P., Bell, D.W., Lake, R., van den Heuvel, S., Settleman, J., Haber, D.A. Cell (2003) [Pubmed]
  2. An isoform of GTPase regulator DOCK4 localizes to the stereocilia in the inner ear and binds to harmonin (USH1C). Yan, D., Li, F., Hall, M.L., Sage, C., Hu, W.H., Giallourakis, C., Upadhyay, G., Ouyang, X.M., Du, L.L., Bethea, J.R., Chen, Z.Y., Yajnik, V., Liu, X.Z. J. Mol. Biol. (2006) [Pubmed]
  3. Dock4 is regulated by RhoG and promotes Rac-dependent cell migration. Hiramoto, K., Negishi, M., Katoh, H. Exp. Cell Res. (2006) [Pubmed]
  4. Finer delineation and transcript map of the 7q31 locus deleted in myeloid neoplasms. Liang, H., Castro, P.D., Ma, J., Nagarajan, L. Cancer Genet. Cytogenet. (2005) [Pubmed]
  5. Evaluation of PMF scoring in docking weak ligands to the FK506 binding protein. Muegge, I., Martin, Y.C., Hajduk, P.J., Fesik, S.W. J. Med. Chem. (1999) [Pubmed]
  6. Evaluation of docking/scoring approaches: a comparative study based on MMP3 inhibitors. Ha, S., Andreani, R., Robbins, A., Muegge, I. J. Comput. Aided Mol. Des. (2000) [Pubmed]
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