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Gene Review

DAB1  -  Dab, reelin signal transducer, homolog 1...

Homo sapiens

Synonyms: Disabled homolog 1
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Disease relevance of DAB1


Psychiatry related information on DAB1

  • In humans, Reelin mutations are associated with brain malformations and mental retardation; mutations in DAB1 have not been identified [5].

High impact information on DAB1


Biological context of DAB1

  • We further determined the cellular expression of the proteins RELN and DAB1 in 50 human brains ranging in age from 10 gestational weeks (GW) to 62 years using immunochemistry [9].
  • Loss of crmp1 in a dab1 heterozygous background led to the disruption of hippocampal lamination, a Reeler-like phenotype [10].
  • Alternative polyadenylation and splicing events generate DAB1 isoforms [5].
  • Yet, the third exons of DAB1 and DAB2 were identical in all available sequences and differed at 10 positions from the exon 3 sequences of B-LBI/B-LBII [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 [11].

Anatomical context of DAB1


Associations of DAB1 with chemical compounds

  • In the Reln(rl/rl) cortex, CRMP1 and Dab1 were expressed at a higher level, yet tyrosine phosphorylated at a lower level [10].
  • The total syntheses of DAB1 (1) and (-)-lentiginosine (2) were concisely accomplished from D-lyxose via regioselective and diastereoselective NHCbz introduction using CSI, chemoselective removal of the Cbz protection, and ring-closing metathesis as key steps [15].
  • The tetra-BOC derivatives 1b and 1c were used to prepare several Polymyxin B derivatives 6-27 at the DAB1 and DAB9-gamma-amine [16].
  • Full-length Dab1 or its phosphotyrosine binding domain alone increased surface levels of APP, as determined by surface protein biotinylation and live cell staining [8].
  • In phase II, povidone-iodine was serially diluted in DAB-1 rather than saline [3].
  • We show that degradation of Dab1 depends on Dab1 phosphorylation at specific tyrosine residues and on the E3 ubiquitin ligase component Cullin 5 (Cul5) [17].

Physical interactions of DAB1

  • This finding explains how the Dab1 PTB domain can simultaneously bind PI and the ApoER2 tail [14].

Other interactions of DAB1

  • In the same samples of temporal cortex, we found a decrease in RELN protein of approximately 50% but no changes in DAB1 protein expression [18].
  • The phylogenetic relationships and patterns of nucleotide substitution were compared for introns and exons of class II major histocompatibility complex (MHC) genes in three datasets: human DRB1, human DQA1, and cyprinid fish DAB1 [19].
  • Together, these data suggest that Dab1 alters trafficking and processing of APP and apoEr2, and this effect is influenced by extracellular ligands [8].
  • This review focuses on two related PTB domain containing adaptor proteins that mediate these divergent lipoprotein receptor responses, ARH (autosomal recessive hypercholesterolemia protein) and Dab1 (disabled-1), and discusses the structural and molecular basis of this different behaviour [20].
  • A ligand for apoEr2, the extracellular matrix protein Reelin, significantly increased the interaction of apoEr2 with Dab1 [8].

Analytical, diagnostic and therapeutic context of DAB1


  1. Differential and epigenetic gene expression profiling identifies frequent disruption of the RELN pathway in pancreatic cancers. Sato, N., Fukushima, N., Chang, R., Matsubayashi, H., Goggins, M. Gastroenterology (2006) [Pubmed]
  2. The reelin pathway components disabled-1 and p35 in gangliogliomas--a mutation and expression analysis. Kam, R., Chen, J., Blümcke, I., Normann, S., Fassunke, J., Elger, C.E., Schramm, J., Wiestler, O.D., Becker, A.J. Neuropathol. Appl. Neurobiol. (2004) [Pubmed]
  3. Optimizing breast pocket irrigation: an in vitro study and clinical implications. Adams, W.P., Conner, W.C., Barton, F.E., Rohrich, R.J. Plast. Reconstr. Surg. (2000) [Pubmed]
  4. Gelsolin gene therapy by retrovirus producer cells for human bladder cancer in nude mice. Tanaka, M., Sazawa, A., Shinohara, N., Kobayashi, Y., Fujioka, Y., Koyanagi, T., Kuzumaki, N. Cancer Gene Ther. (1999) [Pubmed]
  5. The gene encoding disabled-1 (DAB1), the intracellular adaptor of the Reelin pathway, reveals unusual complexity in human and mouse. Bar, I., Tissir, F., Lambert de Rouvroit, C., De Backer, O., Goffinet, A.M. J. Biol. Chem. (2003) [Pubmed]
  6. The adaptor molecule Disabled-2 links the transforming growth factor beta receptors to the Smad pathway. Hocevar, B.A., Smine, A., Xu, X.X., Howe, P.H. EMBO J. (2001) [Pubmed]
  7. Decrease in reelin and glutamic acid decarboxylase67 (GAD67) expression in schizophrenia and bipolar disorder: a postmortem brain study. Guidotti, A., Auta, J., Davis, J.M., Di-Giorgi-Gerevini, V., Dwivedi, Y., Grayson, D.R., Impagnatiello, F., Pandey, G., Pesold, C., Sharma, R., Uzunov, D., Costa, E., DiGiorgi Gerevini, V. Arch. Gen. Psychiatry (2000) [Pubmed]
  8. DAB1 and Reelin Effects on Amyloid Precursor Protein and ApoE Receptor 2 Trafficking and Processing. Hoe, H.S., Tran, T.S., Matsuoka, Y., Howell, B.W., Rebeck, G.W. J. Biol. Chem. (2006) [Pubmed]
  9. Reelin and disabled-1 expression in developing and mature human cortical neurons. Deguchi, K., Inoue, K., Avila, W.E., Lopez-Terrada, D., Antalffy, B.A., Quattrocchi, C.C., Sheldon, M., Mikoshiba, K., D'Arcangelo, G., Armstrong, D.L. J. Neuropathol. Exp. Neurol. (2003) [Pubmed]
  10. Collapsin response mediator protein 1 mediates reelin signaling in cortical neuronal migration. Yamashita, N., Uchida, Y., Ohshima, T., Hirai, S., Nakamura, F., Taniguchi, M., Mikoshiba, K., Honnorat, J., Kolattukudy, P., Thomasset, N., Takei, K., Takahashi, T., Goshima, Y. J. Neurosci. (2006) [Pubmed]
  11. 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]
  12. Disabled-1 mRNA and protein expression in developing human cortex. Meyer, G., De Rouvroit, C.L., Goffinet, A.M., Wahle, P. Eur. J. Neurosci. (2003) [Pubmed]
  13. Reelin expression during embryonic brain development in lacertilian lizards. Goffinet, A.M., Bar, I., Bernier, B., Trujillo, C., Raynaud, A., Meyer, G. J. Comp. Neurol. (1999) [Pubmed]
  14. Origins of peptide selectivity and phosphoinositide binding revealed by structures of disabled-1 PTB domain complexes. Stolt, P.C., Jeon, H., Song, H.K., Herz, J., Eck, M.J., Blacklow, S.C. Structure (Camb.) (2003) [Pubmed]
  15. Regioselective and diastereoselective amination of polybenzyl ethers using chlorosulfonyl isocyanate: total syntheses of 1,4-dideoxy-1,4-imino-D-arabinitol and (-)-lentiginosine. Kim, I.S., Zee, O.P., Jung, Y.H. Org. Lett. (2006) [Pubmed]
  16. Selective chemical modifications of polymyxin B. Weinstein, J., Afonso, A., Moss, E., Miller, G.H. Bioorg. Med. Chem. Lett. (1998) [Pubmed]
  17. Cullin 5 regulates Dab1 protein levels and neuron positioning during cortical development. Feng, L., Allen, N.S., Simo, S., Cooper, J.A. Genes Dev. (2007) [Pubmed]
  18. A decrease of reelin expression as a putative vulnerability factor in schizophrenia. Impagnatiello, F., Guidotti, A.R., Pesold, C., Dwivedi, Y., Caruncho, H., Pisu, M.G., Uzunov, D.P., Smalheiser, N.R., Davis, J.M., Pandey, G.N., Pappas, G.D., Tueting, P., Sharma, R.P., Costa, E. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  19. Evolution of introns and exons of class II major histocompatibility complex genes of vertebrates. Hughes, A.L. Immunogenetics (2000) [Pubmed]
  20. Modulation of lipoprotein receptor functions by intracellular adaptor proteins. Stolt, P.C., Bock, H.H. Cell. Signal. (2006) [Pubmed]
  21. The reelin signaling pathway: some recent developments. Jossin, Y., Bar, I., Ignatova, N., Tissir, F., De Rouvroit, C.L., Goffinet, A.M. Cereb. Cortex (2003) [Pubmed]
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