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Gene Review

DAB2  -  Dab, mitogen-responsive phosphoprotein,...

Homo sapiens

Synonyms: Adaptor molecule disabled-2, DOC-2, DOC2, Differentially expressed in ovarian carcinoma 2, Differentially-expressed protein 2, ...
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Disease relevance of DAB2


High impact information on DAB2

  • In vivo targeting and recruitment of myosin VI to clathrin-coated structures (CCSs) at the plasma membrane is mediated by Dab2 and PtdIns(4,5)P(2) binding [7].
  • DOC2 proteins constitute a novel protein family that may function in secretion and contain a double C2 domain [8].
  • These data suggest that DOC2 proteins are vesicular adapter proteins regulating munc18-syntaxin complexes and herewith synaptic vesicle docking [8].
  • Dab2 could be conditionally deleted from the embryo without affecting normal development, showing that Dab2 is required in the visceral endoderm but dispensable in the embryo proper [9].
  • Dual roles for the Dab2 adaptor protein in embryonic development and kidney transport [9].

Biological context of DAB2


Anatomical context of DAB2


Associations of DAB2 with chemical compounds

  • In this study, the role of DAB2 in integrin alpha(IIb)beta(3)-mediated matrix protein fibrinogen adhesion and cell signaling was investigated [10].
  • DAB2 induction and megakaryocytic differentiation was abrogated when cells were co-treated with the PDGF receptor inhibitor STI571 or when the conditioned medium was derived from TPA-plus STI571-treated cells [12].
  • The secreted DAB2 binds to the extracellular region of alphaIIbbeta3 integrin on the platelet surface through the phosphotyrosine-binding domain [16].
  • Biochemical and mutational analysis revealed that the DAB2 cell-adhesion Arg-Gly-Asp (RGD) motif (amino acid residues 64-66) and the alphaIIb-integrin-fibrinogen-binding region (amino acid residues 171-464) are important for the DAB2-platelet interactions [16].
  • On the other hand, the differentiation agents DMSO and retinoic acid had no effect on DAB2 expression [17].

Physical interactions of DAB2

  • The present findings suggest that myosin VI plays a role in transporting DOC-2/DAB2, a Ras cascade signaling molecule, thus involved in Ras signaling pathways [18].
  • It appears that DOC-2/DAB2 can bind to Src homology 3 domain of c-Src and maintain it in an inactive conformation [1].

Enzymatic interactions of DAB2

  • These findings reveal that Dab2 is differentially phosphorylated during the cell cycle by cdc2 and provide a potential feedback mechanism by which Dab2 inhibition of cell growth and proliferation may be regulated [19].

Regulatory relationships of DAB2


Other interactions of DAB2

  • We describe the cloning of DIP1/2, a novel gene that interacts with the N-terminal domain of DOC-2/DAB2 [22].
  • Hence, DAB2 elicits distinct regulatory mechanisms in alpha(IIb)beta(3) and beta-catenin/plakoglobin signaling in a Ser(24) phosphorylation-dependent and -independent manner, respectively [10].
  • Using a synthetic Ser(24) peptide (APS(24)KKEKKKGSEKTD) or recombinant DOC-2/DAB2 as substrates, PKCbetaII, PKCgamma, and PKCdelta (but not casein kinase II) directly phosphorylated Ser(24) in vitro [11].
  • Given the divergence in the 3'UT region, the finding of the same exon 2 sequence at both the DAB1 and the DAB2 loci in one of the pheasant haplotypes also suggests that interlocus genetic exchange does occur [23].
  • The C-terminal domain but not the N-terminal domain of DOC-2/DAB2 functions as a myosin VI anchoring site [18].

Analytical, diagnostic and therapeutic context of DAB2

  • Through cellular localization and co-immunoprecipitation analysis, we demonstrate for the first time that Ser(24) phosphorylation promotes membrane translocation of DAB2 and its subsequent interaction with integrin beta(3), thereby defining a mechanism for DAB2 in regulating integrin alpha(IIb)beta(3) activation and inside-out signaling [10].
  • Western blot analysis revealed that conditioned medium from 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated, megakaryocytic differentiating K562 cells upregulated DAB2 expression [12].
  • We evaluated 24 normal and malignant bladder specimens for retinoid receptor, DAB2 and Midkine mRNA expression using RT-PCR [24].
  • METHODS: DAB2 expression was analyzed by immunohistochemistry in 50 primary esophageal squamous cell carcinomas (ESCCs), 30 distinct hyperplasia, 15 dysplasia and 10 non-malignant esophageal tissues [25].
  • To determine whether promoter hypermethylation contributes to loss of DAB2 expression in ESCCs, methylation status of DAB2 promoter was analyzed in DAB2 immuno-negative tumors using methylation-specific PCR [25].


  1. Characterization of a novel negative regulator (DOC-2/DAB2) of c-Src in normal prostatic epithelium and cancer. Zhou, J., Scholes, J., Hsieh, J.T. J. Biol. Chem. (2003) [Pubmed]
  2. Aberrant promoter methylation in human DAB2 interactive protein (hDAB2IP) gene in breast cancer. Dote, H., Toyooka, S., Tsukuda, K., Yano, M., Ouchida, M., Doihara, H., Suzuki, M., Chen, H., Hsieh, J.T., Gazdar, A.F., Shimizu, N. Clin. Cancer Res. (2004) [Pubmed]
  3. Aberrant promoter methylation of human DAB2 interactive protein (hDAB2IP) gene in lung cancers. Yano, M., Toyooka, S., Tsukuda, K., Dote, H., Ouchida, M., Hanabata, T., Aoe, M., Date, H., Gazdar, A.F., Shimizu, N. Int. J. Cancer (2005) [Pubmed]
  4. Transfer of chromosome 3 fragments suppresses tumorigenicity of an ovarian cancer cell line monoallelic for chromosome 3p. Cody, N.A., Ouellet, V., Manderson, E.N., Quinn, M.C., Filali-Mouhim, A., Tellis, P., Zietarska, M., Provencher, D.M., Mes-Masson, A.M., Chevrette, M., Tonin, P.N. Oncogene (2007) [Pubmed]
  5. Synergistic induction of DOC-2/DAB2 gene expression in transitional cell carcinoma in the presence of GATA6 and histone deacetylase inhibitor. Zhou, J., Hernandez, G., Tu, S.W., Scholes, J., Chen, H., Tseng, C.P., Hsieh, J.T. Cancer Res. (2005) [Pubmed]
  6. Decreased DOC-2/DAB2 expression in urothelial carcinoma of the bladder. Karam, J.A., Shariat, S.F., Huang, H.Y., Pong, R.C., Ashfaq, R., Shapiro, E., Lotan, Y., Sagalowsky, A.I., Wu, X.R., Hsieh, J.T. Clin. Cancer Res. (2007) [Pubmed]
  7. Myosin VI targeting to clathrin-coated structures and dimerization is mediated by binding to Disabled-2 and PtdIns(4,5)P(2). Spudich, G., Chibalina, M.V., Au, J.S., Arden, S.D., Buss, F., Kendrick-Jones, J. Nat. Cell Biol. (2007) [Pubmed]
  8. DOC2 proteins in rat brain: complementary distribution and proposed function as vesicular adapter proteins in early stages of secretion. Verhage, M., de Vries, K.J., Røshol, H., Burbach, J.P., Gispen, W.H., Südhof, T.C. Neuron (1997) [Pubmed]
  9. Dual roles for the Dab2 adaptor protein in embryonic development and kidney transport. Morris, S.M., Tallquist, M.D., Rock, C.O., Cooper, J.A. EMBO J. (2002) [Pubmed]
  10. Disabled-2 is a negative regulator of integrin alpha(IIb)beta(3)-mediated fibrinogen adhesion and cell signaling. Huang, C.L., Cheng, J.C., Liao, C.H., Stern, A., Hsieh, J.T., Wang, C.H., Hsu, H.L., Tseng, C.P. J. Biol. Chem. (2004) [Pubmed]
  11. The role of DOC-2/DAB2 protein phosphorylation in the inhibition of AP-1 activity. An underlying mechanism of its tumor-suppressive function in prostate cancer. Tseng, C.P., Ely, B.D., Pong, R.C., Wang, Z., Zhou, J., Hsieh, J.T. J. Biol. Chem. (1999) [Pubmed]
  12. Autocrine signaling of platelet-derived growth factor regulates disabled-2 expression during megakaryocytic differentiation of K562 cells. Tseng, C.P., Chang, P., Huang, C.L., Cheng, J.C., Chang, S.S. FEBS Lett. (2005) [Pubmed]
  13. Inhibition of Mitogen-Elicited Signal Transduction and Growth in Prostate Cancer with a Small Peptide Derived from the Functional Domain of DOC-2/DAB2 Delivered by a Unique Vehicle. Zhou, J., Fan, J., Hsieh, J.T. Cancer Res. (2006) [Pubmed]
  14. Myosin VI binds to and localises with Dab2, potentially linking receptor-mediated endocytosis and the actin cytoskeleton. Morris, S.M., Arden, S.D., Roberts, R.C., Kendrick-Jones, J., Cooper, J.A., Luzio, J.P., Buss, F. Traffic (2002) [Pubmed]
  15. The putative human stem cell marker, Rex-1 (Zfp42): Structural classification and expression in normal human epithelial and carcinoma cell cultures. Mongan, N.P., Martin, K.M., Gudas, L.J. Mol. Carcinog. (2006) [Pubmed]
  16. Disabled-2 is a novel {alpha}IIb-integrin-binding protein that negatively regulates platelet-fibrinogen interactions and platelet aggregation. Huang, C.L., Cheng, J.C., Stern, A., Hsieh, J.T., Liao, C.H., Tseng, C.P. J. Cell. Sci. (2006) [Pubmed]
  17. Induction of disabled-2 gene during megakaryocyte differentiation of k562 cells. Tseng, C.P., Huang, C.H., Tseng, C.C., Lin, M.H., Hsieh, J.T., Tseng, C.H. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  18. DOC-2/DAB2 is the binding partner of myosin VI. Inoue, A., Sato, O., Homma, K., Ikebe, M. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  19. Cell cycle-dependent phosphorylation of Disabled-2 by cdc2. He, J., Xu, J., Xu, X.X., Hall, R.A. Oncogene (2003) [Pubmed]
  20. Regulation of myosin-VI targeting to endocytic compartments. Dance, A.L., Miller, M., Seragaki, S., Aryal, P., White, B., Aschenbrenner, L., Hasson, T. Traffic (2004) [Pubmed]
  21. DOC-2/hDab-2 inhibits ILK activity and induces anoikis in breast cancer cells through an Akt-independent pathway. Wang, S.C., Makino, K., Xia, W., Kim, J.S., Im, S.A., Peng, H., Mok, S.C., Singletary, S.E., Hung, M.C. Oncogene (2001) [Pubmed]
  22. The mechanism of growth-inhibitory effect of DOC-2/DAB2 in prostate cancer. Characterization of a novel GTPase-activating protein associated with N-terminal domain of DOC-2/DAB2. Wang, Z., Tseng, C.P., Pong, R.C., Chen, H., McConnell, J.D., Navone, N., Hsieh, J.T. J. Biol. Chem. (2002) [Pubmed]
  23. Concerted evolution of two Mhc class II B loci in pheasants and domestic chickens. Wittzell, H., Bernot, A., Auffray, C., Zoorob, R. Mol. Biol. Evol. (1999) [Pubmed]
  24. Retinoid receptor mRNA expression profiles in human bladder cancer specimens. Boorjian, S., Scherr, D.S., Mongan, N.P., Zhuang, Y., Nanus, D.M., Gudas, L.J. Int. J. Oncol. (2005) [Pubmed]
  25. Loss of disabled-2 expression is an early event in esophageal squamous tumorigenesis. Anupam, K., Tusharkant, C., Gupta, S.D., Ranju, R. World J. Gastroenterol. (2006) [Pubmed]
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