DAB2

DAB2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2LSW
Identifiers
Aliases	DAB2 , DOC-2, DOC2, clathrin adaptor protein, DAB adaptor protein 2
External IDs	OMIM: 601236 MGI: 109175 HomoloGene: 1026 GeneCards: DAB2
Gene location (Human) Chr. Chromosome 5 (human) [1] Band 5p13.1 Start 39,371,675 bp [1] End 39,462,300 bp [1]
Gene location (Mouse) Chr. Chromosome 15 (mouse) [2] Band 15 A1|15 2.15 cM Start 6,329,269 bp [2] End 6,470,193 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in caput epididymis corpus epididymis placenta synovial joint Achilles tendon kidney synovial membrane left adrenal gland renal medulla germinal epithelium Top expressed in yolk sac kidney dermis adrenal gland proximal tubule secondary oocyte ankle aortic valve calvaria primitive streak More reference expression data BioGPS More reference expression data
Gene ontology Molecular function clathrin adaptor activity protein C-terminus binding protein binding cargo receptor activity SMAD binding Cellular component cytoplasm intracellular membrane-bounded organelle membrane focal adhesion plasma membrane lysosomal membrane nucleolus clathrin-coated vesicle membrane clathrin-coated pit extracellular exosome cytoplasmic vesicle clathrin-coated vesicle fibrillar center cytosol Biological process positive regulation of transforming growth factor beta receptor signaling pathway cell differentiation positive regulation of protein phosphorylation endocytosis positive regulation of cell migration positive regulation of pathway-restricted SMAD protein phosphorylation negative regulation of androgen receptor signaling pathway negative regulation of apoptotic process Wnt signaling pathway negative regulation of protein binding positive regulation of epithelial to mesenchymal transition leading edge cell differentiation multicellular organism development positive regulation of transcription, DNA-templated positive regulation of endocytosis negative regulation of protein localization to plasma membrane positive regulation of clathrin-dependent endocytosis protein transport positive regulation of early endosome to late endosome transport integrin-mediated signaling pathway positive regulation of Wnt signaling pathway, planar cell polarity pathway cell population proliferation negative regulation of transcription, DNA-templated negative regulation of canonical Wnt signaling pathway positive regulation of proteasomal ubiquitin-dependent protein catabolic process positive regulation of SMAD protein signal transduction apoptotic process receptor-mediated endocytosis membrane organization transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1601 13132 Ensembl ENSG00000153071 ENSMUSG00000022150 UniProt P98082 P98078 RefSeq (mRNA) NM_001343 NM_001244871 NM_001008702 NM_001037905 NM_001102400 NM_023118 NM_001310446 RefSeq (protein) NP_001231800 NP_001334 NP_001008702 NP_001032994 NP_001095870 NP_001297375 NP_075607 Location (UCSC) Chr 5: 39.37 – 39.46 Mb Chr 15: 6.33 – 6.47 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Disabled homolog 2 is a protein that in humans is encoded by the DAB2 gene. ^{[5] [6]}

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). ^[7]

Interactions

DAB2 has been shown to interact with:

• C-src tyrosine kinase, ^[8]
• Cdk1, ^[9]
• DAB2IP, ^[10]
• DVL2, ^[11]
• DVL3, ^[11]
• LRP2, ^[12]
• MYO6, ^{[13] [14]}
• Mothers against decapentaplegic homolog 2, ^[15]
• Mothers against decapentaplegic homolog 3 ^[15]
• PIN1, ^[9] and
• Src. ^[8]

References

1. GRCh38: Ensembl release 89: ENSG00000153071 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000022150 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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.
6. 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.
7. "Entrez Gene: DAB2 disabled homolog 2, mitogen-responsive phosphoprotein (Drosophila)".
8. 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.
9. 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.
10. 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.
11. 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.
12. 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 (3): 613–21. doi:10.1042/0264-6021:3470613. PMC   1220996 . PMID   10769163.
13. 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. S2CID   25079713.
14. 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.
15. 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. S2CID   33186168.
• 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. S2CID   25079713.
• 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. Bibcode:2003PNAS..100.2272C. doi: 10.1073/pnas.262791999 . PMC   151330 . PMID   12606711.