DAB2

Dab, mitogen-responsive phosphoprotein, homolog 2 (Drosophila)
PDB rendering based on 1m7e.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2LSW​
Identifiers
Symbols	DAB2 ; DOC-2; DOC2
External IDs	OMIM: 601236 MGI: 109175 HomoloGene: 1026 GeneCards: DAB2 Gene
Gene ontology Molecular function • protein binding • protein C-terminus binding • clathrin adaptor activity • cargo receptor activity • SMAD binding Cellular component • nucleolus • lysosomal membrane • plasma membrane • coated pit • focal adhesion • clathrin-coated vesicle • clathrin-coated vesicle membrane • intracellular membrane-bounded organelle • transforming growth factor beta receptor homodimeric complex • extracellular exosome Biological process • positive regulation of protein phosphorylation • receptor-mediated endocytosis • apoptotic process • integrin-mediated signaling pathway • multicellular organismal development • cell proliferation • positive regulation of epithelial to mesenchymal transition • positive regulation of pathway-restricted SMAD protein phosphorylation • protein transport • Wnt signaling pathway • positive regulation of cell migration • positive regulation of transforming growth factor beta receptor signaling pathway • negative regulation of protein binding • positive regulation of proteasomal ubiquitin-dependent protein catabolic process • leading edge cell differentiation • negative regulation of apoptotic process • positive regulation of endocytosis • negative regulation of transcription, DNA-templated • positive regulation of transcription, DNA-templated • positive regulation of SMAD protein import into nucleus • negative regulation of androgen receptor signaling pathway • membrane organization • negative regulation of canonical Wnt signaling pathway • negative regulation of protein localization to plasma membrane • positive regulation of Wnt signaling pathway, planar cell polarity pathway • positive regulation of clathrin-mediated endocytosis • positive regulation of early endosome to late endosome transport Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	1601	13132
Ensembl	ENSG00000153071	ENSMUSG00000022150
UniProt	P98082	P98078
RefSeq (mRNA)	NM_001244871	NM_001008702
RefSeq (protein)	NP_001231800	NP_001008702
Location (UCSC)	Chr 5: 39.37 – 39.46 Mb	Chr 15: 6.3 – 6.44 Mb
PubMed search

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

1. Albertsen HM, Smith SA, Melis R, Williams B, Holik P, Stevens J, White R (January 1997). "Sequence, genomic structure, and chromosomal assignment of human DOC-2". Genomics 33 (2): 207–13. doi:10.1006/geno.1996.0185. PMID 8660969.
2. Mok SC, Chan WY, Wong KK, Cheung KK, Lau CC, Ng SW, Baldini A, Colitti CV, Rock CO, Berkowitz RS (June 1998). "DOC-2, a candidate tumor suppressor gene in human epithelial ovarian cancer". Oncogene 16 (18): 2381–7. doi:10.1038/sj.onc.1201769. PMID 9620555.
3. "Entrez Gene: DAB2 disabled homolog 2, mitogen-responsive phosphoprotein (Drosophila)".
4. Zhou J, Scholes J, Hsieh JT (February 2003). "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. doi:10.1074/jbc.M210628200. PMID 12473651.
5. He J, Xu J, Xu XX, Hall RA (July 2003). "Cell cycle-dependent phosphorylation of Disabled-2 by cdc2". Oncogene 22 (29): 4524–30. doi:10.1038/sj.onc.1206767. PMID 12881709.
6. Wang Z, Tseng CP, Pong RC, Chen H, McConnell JD, Navone N, Hsieh JT (April 2002). "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. doi:10.1074/jbc.M110568200. PMID 11812785.
7. Hocevar BA, Mou F, Rennolds JL, Morris SM, Cooper JA, Howe PH (June 2003). "Regulation of the Wnt signaling pathway by disabled-2 (Dab2)". EMBO J. 22 (12): 3084–94. doi:10.1093/emboj/cdg286. PMC 162138. PMID 12805222.
8. Oleinikov AV, Zhao J, Makker SP (May 2000). "Cytosolic adaptor protein Dab2 is an intracellular ligand of endocytic receptor gp600/megalin". Biochem. J. 347 Pt 3: 613–21. doi:10.1042/0264-6021:3470613. PMC 1220996. PMID 10769163.
9. Morris SM, Arden SD, Roberts RC, Kendrick-Jones J, Cooper JA, Luzio JP, Buss F (May 2002). "Myosin VI binds to and localises with Dab2, potentially linking receptor-mediated endocytosis and the actin cytoskeleton". Traffic 3 (5): 331–41. doi:10.1034/j.1600-0854.2002.30503.x. PMID 11967127.
10. Inoue A, Sato O, Homma K, Ikebe M (March 2002). "DOC-2/DAB2 is the binding partner of myosin VI". Biochem. Biophys. Res. Commun. 292 (2): 300–7. doi:10.1006/bbrc.2002.6636. PMID 11906161.
11. Hocevar BA, Smine A, Xu XX, Howe PH (June 2001). "The adaptor molecule Disabled-2 links the transforming growth factor beta receptors to the Smad pathway". EMBO J. 20 (11): 2789–801. doi:10.1093/emboj/20.11.2789. PMC 125498. PMID 11387212.

Further reading

• Mok SC, Wong KK, Chan RK, Lau CC, Tsao SW, Knapp RC, Berkowitz RS (1994). "Molecular cloning of differentially expressed genes in human epithelial ovarian cancer". Gynecol. Oncol. 52 (2): 247–52. doi:10.1006/gyno.1994.1040. PMID 8314147.
• Bonaldo MF, Lennon G, Soares MB (1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
• Xu XX, Yi T, Tang B, Lambeth JD (1998). "Disabled-2 (Dab2) is an SH3 domain-binding partner of Grb2". Oncogene 16 (12): 1561–9. doi:10.1038/sj.onc.1201678. PMID 9569023.
• Fazili Z, Sun W, Mittelstaedt S, Cohen C, Xu XX (1999). "Disabled-2 inactivation is an early step in ovarian tumorigenicity". Oncogene 18 (20): 3104–13. doi:10.1038/sj.onc.1202649. PMID 10340382.
• Tseng CP, Ely BD, Pong RC, Wang Z, Zhou J, Hsieh JT (1999). "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. doi:10.1074/jbc.274.45.31981. PMID 10542228.
• Oleinikov AV, Zhao J, Makker SP (2000). "Cytosolic adaptor protein Dab2 is an intracellular ligand of endocytic receptor gp600/megalin". Biochem. J. 347 Pt 3 (3): 613–21. doi:10.1042/0264-6021:3470613. PMC 1220996. PMID 10769163.
• Sheng Z, Sun W, Smith E, Cohen C, Sheng Z, Xu XX (2000). "Restoration of positioning control following Disabled-2 expression in ovarian and breast tumor cells". Oncogene 19 (42): 4847–54. doi:10.1038/sj.onc.1203853. PMID 11039902.
• Sheng Z, He J, Tuppen JA, Sun W, Fazili Z, Smith ER, Dong FB, Xu XX (2000). "Structure, sequence, and promoter analysis of human disabled-2 gene (DAB2)". Genomics 70 (3): 381–6. doi:10.1006/geno.2000.6383. PMID 11161789.
• Morris SM, Cooper JA (2001). "Disabled-2 colocalizes with the LDLR in clathrin-coated pits and interacts with AP-2". Traffic 2 (2): 111–23. doi:10.1034/j.1600-0854.2001.020206.x. PMID 11247302.
• Zhou J, Hsieh JT (2001). "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. doi:10.1074/jbc.M102803200. PMID 11371563.
• Hocevar BA, Smine A, Xu XX, Howe PH (2001). "The adaptor molecule Disabled-2 links the transforming growth factor beta receptors to the Smad pathway". EMBO J. 20 (11): 2789–801. doi:10.1093/emboj/20.11.2789. PMC 125498. PMID 11387212.
• Wang Z, Tseng CP, Pong RC, Chen H, McConnell JD, Navone N, Hsieh JT (2002). "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. doi:10.1074/jbc.M110568200. PMID 11812785.
• Inoue A, Sato O, Homma K, Ikebe M (2002). "DOC-2/DAB2 is the binding partner of myosin VI". Biochem. Biophys. Res. Commun. 292 (2): 300–7. doi:10.1006/bbrc.2002.6636. PMID 11906161.
• Mishra SK, Keyel PA, Hawryluk MJ, Agostinelli NR, Watkins SC, Traub LM (2002). "Disabled-2 exhibits the properties of a cargo-selective endocytic clathrin adaptor". EMBO J. 21 (18): 4915–26. doi:10.1093/emboj/cdf487. PMC 126284. PMID 12234931.
• Morris SM, Tallquist MD, Rock CO, Cooper JA (2002). "Dual roles for the Dab2 adaptor protein in embryonic development and kidney transport". EMBO J. 21 (7): 1555–64. doi:10.1093/emboj/21.7.1555. PMC 125955. PMID 11927540.
• Morris SM, Arden SD, Roberts RC, Kendrick-Jones J, Cooper JA, Luzio JP, Buss F (2002). "Myosin VI binds to and localises with Dab2, potentially linking receptor-mediated endocytosis and the actin cytoskeleton". Traffic 3 (5): 331–41. doi:10.1034/j.1600-0854.2002.30503.x. PMID 11967127.
• Zhou J, Scholes J, Hsieh JT (2003). "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. doi:10.1074/jbc.M210628200. PMID 12473651.
• Calderwood DA, Fujioka Y, de Pereda JM, García-Alvarez B, Nakamoto T, Margolis B, McGlade CJ, Liddington RC, Ginsberg MH (2003). "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. doi:10.1073/pnas.262791999. PMC 151330. PMID 12606711.