Biology:DAB2
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Short description: Protein-coding gene in the species Homo sapiens
 Generic protein structure example |
Disabled homolog 2 is a protein that in humans is encoded by the DAB2 gene.[1][2]
Function
DAB2 mRNA is expressed in normal ovarian epithelial cells but is down-regulated or absent from ovarian carcinoma cell lines. The 770-amino acid predicted protein has an overall 83% identity with the mouse p96 protein, a putative mitogen-responsive phosphoprotein; homology is strongest in the amino-terminal end of the protein in a region corresponding to the phosphotyrosine interaction domain. The down-regulation of DAB2 may play an important role in ovarian carcinogenesis. This gene was initially named DOC2 (for Differentially expressed in Ovarian Cancer) and is distinct from the DOC2A and DOC2B genes (for double C2-like domains, alpha and beta).[3]
Interactions
DAB2 has been shown to interact with:
- C-src tyrosine kinase,[4]
- Cdk1,[5]
- DAB2IP,[6]
- DVL2,[7]
- DVL3,[7]
- LRP2,[8]
- MYO6,[9][10]
- Mothers against decapentaplegic homolog 2,[11]
- Mothers against decapentaplegic homolog 3[11]
- PIN1,[5] and
- Src.[4]
References
- ↑ "Sequence, genomic structure, and chromosomal assignment of human DOC-2". Genomics 33 (2): 207–13. January 1997. doi:10.1006/geno.1996.0185. PMID 8660969.
- ↑ "DOC-2, a candidate tumor suppressor gene in human epithelial ovarian cancer". Oncogene 16 (18): 2381–7. June 1998. doi:10.1038/sj.onc.1201769. PMID 9620555.
- ↑ "Entrez Gene: DAB2 disabled homolog 2, mitogen-responsive phosphoprotein (Drosophila)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1601.
- ↑ 4.0 4.1 "Characterization of a novel negative regulator (DOC-2/DAB2) of c-Src in normal prostatic epithelium and cancer". J. Biol. Chem. 278 (9): 6936–41. February 2003. doi:10.1074/jbc.M210628200. PMID 12473651.
- ↑ 5.0 5.1 "Cell cycle-dependent phosphorylation of Disabled-2 by cdc2". Oncogene 22 (29): 4524–30. July 2003. doi:10.1038/sj.onc.1206767. PMID 12881709.
- ↑ "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". J. Biol. Chem. 277 (15): 12622–31. April 2002. doi:10.1074/jbc.M110568200. PMID 11812785.
- ↑ 7.0 7.1 "Regulation of the Wnt signaling pathway by disabled-2 (Dab2)". EMBO J. 22 (12): 3084–94. June 2003. doi:10.1093/emboj/cdg286. PMID 12805222.
- ↑ "Cytosolic adaptor protein Dab2 is an intracellular ligand of endocytic receptor gp600/megalin". Biochem. J. 347 Pt 3 (3): 613–21. May 2000. doi:10.1042/0264-6021:3470613. PMID 10769163.
- ↑ "Myosin VI binds to and localises with Dab2, potentially linking receptor-mediated endocytosis and the actin cytoskeleton". Traffic 3 (5): 331–41. May 2002. doi:10.1034/j.1600-0854.2002.30503.x. PMID 11967127.
- ↑ "DOC-2/DAB2 is the binding partner of myosin VI". Biochem. Biophys. Res. Commun. 292 (2): 300–7. March 2002. doi:10.1006/bbrc.2002.6636. PMID 11906161.
- ↑ 11.0 11.1 "The adaptor molecule Disabled-2 links the transforming growth factor beta receptors to the Smad pathway". EMBO J. 20 (11): 2789–801. June 2001. doi:10.1093/emboj/20.11.2789. PMID 11387212.
Further reading
- "Molecular cloning of differentially expressed genes in human epithelial ovarian cancer". Gynecol. Oncol. 52 (2): 247–52. 1994. doi:10.1006/gyno.1994.1040. PMID 8314147.
- "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. 1996. doi:10.1101/gr.6.9.791. PMID 8889548.
- "Disabled-2 (Dab2) is an SH3 domain-binding partner of Grb2". Oncogene 16 (12): 1561–9. 1998. doi:10.1038/sj.onc.1201678. PMID 9569023.
- "Disabled-2 inactivation is an early step in ovarian tumorigenicity". Oncogene 18 (20): 3104–13. 1999. doi:10.1038/sj.onc.1202649. PMID 10340382.
- "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". J. Biol. Chem. 274 (45): 31981–6. 1999. doi:10.1074/jbc.274.45.31981. PMID 10542228.
- "Cytosolic adaptor protein Dab2 is an intracellular ligand of endocytic receptor gp600/megalin". Biochem. J. 347 Pt 3 (3): 613–21. 2000. doi:10.1042/0264-6021:3470613. PMID 10769163.
- "Restoration of positioning control following Disabled-2 expression in ovarian and breast tumor cells". Oncogene 19 (42): 4847–54. 2000. doi:10.1038/sj.onc.1203853. PMID 11039902.
- "Structure, sequence, and promoter analysis of human disabled-2 gene (DAB2)". Genomics 70 (3): 381–6. 2000. doi:10.1006/geno.2000.6383. PMID 11161789.
- "Disabled-2 colocalizes with the LDLR in clathrin-coated pits and interacts with AP-2". Traffic 2 (2): 111–23. 2001. doi:10.1034/j.1600-0854.2001.020206.x. PMID 11247302.
- "The inhibitory role of DOC-2/DAB2 in growth factor receptor-mediated signal cascade. DOC-2/DAB2-mediated inhibition of ERK phosphorylation via binding to Grb2". J. Biol. Chem. 276 (30): 27793–8. 2001. doi:10.1074/jbc.M102803200. PMID 11371563.
- "The adaptor molecule Disabled-2 links the transforming growth factor beta receptors to the Smad pathway". EMBO J. 20 (11): 2789–801. 2001. doi:10.1093/emboj/20.11.2789. PMID 11387212.
- "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". J. Biol. Chem. 277 (15): 12622–31. 2002. doi:10.1074/jbc.M110568200. PMID 11812785.
- "DOC-2/DAB2 is the binding partner of myosin VI". Biochem. Biophys. Res. Commun. 292 (2): 300–7. 2002. doi:10.1006/bbrc.2002.6636. PMID 11906161.
- "Disabled-2 exhibits the properties of a cargo-selective endocytic clathrin adaptor". EMBO J. 21 (18): 4915–26. 2002. doi:10.1093/emboj/cdf487. PMID 12234931.
- "Dual roles for the Dab2 adaptor protein in embryonic development and kidney transport". EMBO J. 21 (7): 1555–64. 2002. doi:10.1093/emboj/21.7.1555. PMID 11927540.
- "Myosin VI binds to and localises with Dab2, potentially linking receptor-mediated endocytosis and the actin cytoskeleton". Traffic 3 (5): 331–41. 2002. doi:10.1034/j.1600-0854.2002.30503.x. PMID 11967127.
- "Characterization of a novel negative regulator (DOC-2/DAB2) of c-Src in normal prostatic epithelium and cancer". J. Biol. Chem. 278 (9): 6936–41. 2003. doi:10.1074/jbc.M210628200. PMID 12473651.
- "Integrin beta cytoplasmic domain interactions with phosphotyrosine-binding domains: a structural prototype for diversity in integrin signaling". Proc. Natl. Acad. Sci. U.S.A. 100 (5): 2272–7. 2003. doi:10.1073/pnas.262791999. PMID 12606711. Bibcode: 2003PNAS..100.2272C.
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