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Showing Protein Disabled homolog 2 (HMDBP14528)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 1 metabolite
Identification
HMDB Protein ID HMDBP14528
Secondary Accession Numbers None
Name Disabled homolog 2
Synonyms
  1. Adaptor molecule disabled-2
  2. C9
  3. Differentially expressed in ovarian carcinoma 2
  4. Mitogen-responsive phosphoprotein
  5. DOC-2
Gene Name DAB2
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function Adapter protein that functions as clathrin-associated sorting protein (CLASP) required for clathrin-mediated endocytosis of selected cargo proteins. Can bind and assemble clathrin, and binds simultaneously to phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and cargos containing non-phosphorylated NPXY internalization motifs, such as the LDL receptor, to recruit them to clathrin-coated pits. Can function in clathrin-mediated endocytosis independently of the AP-2 complex. Involved in endocytosis of integrin beta-1; this function seems to redundant with the AP-2 complex and seems to require DAB2 binding to endocytosis accessory EH domain-containing proteins such as EPS15, EPS15L1 and ITSN1. Involved in endocytosis of cystic fibrosis transmembrane conductance regulator/CFTR. Involved in endocytosis of megalin/LRP2 lipoprotein receptor during embryonal development. Required for recycling of the TGF-beta receptor. Involved in CFTR trafficking to the late endosome. Involved in several receptor-mediated signaling pathways. Involved in TGF-beta receptor signaling and facilitates phosphorylation of the signal transducer SMAD2. Mediates TFG-beta-stimulated JNK activation. May inhibit the canoniocal Wnt/beta-catenin signaling pathway by stabilizing the beta-catenin destruction complex through a competing association with axin preventing its dephosphorylation through protein phosphatase 1 (PP1). Sequesters LRP6 towards clathrin-mediated endocytosis, leading to inhibition of Wnt/beta-catenin signaling. May activate non-canonical Wnt signaling. In cell surface growth factor/Ras signaling pathways proposed to inhibit ERK activation by interrupting the binding of GRB2 to SOS1 and to inhibit SRC by preventing its activating phosphorylation at 'Tyr-419'. Proposed to be involved in modulation of androgen receptor (AR) signaling mediated by SRC activation; seems to compete with AR for interaction with SRC. Plays a role in the CSF-1 signal transduction pathway. Plays a role in cellular differentiation. Involved in cell positioning and formation of visceral endoderm (VE) during embryogenesis and proposed to be required in the VE to respond to Nodal signaling coming from the epiblast. Required for the epithelial to mesenchymal transition, a process necessary for proper embryonic development. May be involved in myeloid cell differentiation and can induce macrophage adhesion and spreading. May act as a tumor suppressor.
Pathways
  • Endocytosis
Reactions Not Available
GO Classification
Biological Process
pinocytosis
positive regulation of transcription elongation from RNA polymerase II promoter
positive regulation of cell migration
apoptotic process
negative regulation of apoptotic process
positive regulation of cell adhesion
protein transport
negative regulation of epithelial cell proliferation
in utero embryonic development
negative regulation of extrinsic apoptotic signaling pathway
positive regulation of pathway-restricted SMAD protein phosphorylation
positive regulation of epithelial to mesenchymal transition
positive regulation of integrin-mediated signaling pathway
activation of JUN kinase activity
Wnt receptor signaling pathway
positive regulation of endocytosis
cellular response to epidermal growth factor stimulus
endoderm development
negative regulation of canonical Wnt receptor signaling pathway
negative regulation of neuron projection development
negative regulation of cell growth
positive regulation of receptor internalization
positive regulation of aldosterone biosynthetic process
positive regulation of aldosterone secretion
response to steroid hormone stimulus
negative regulation of protein localization to plasma membrane
negative regulation of ERK1 and ERK2 cascade
response to salt
cellular response to transforming growth factor beta stimulus
excretion
cell morphogenesis involved in differentiation
clathrin coat assembly
hematopoietic stem cell proliferation
positive regulation of clathrin-dependent endocytosis
regulation of Rho-dependent protein serine/threonine kinase activity
receptor-mediated endocytosis
myeloid cell differentiation
positive regulation of substrate adhesion-dependent cell spreading
positive regulation of receptor recycling
Cellular Component
cytoplasm
plasma membrane
perinuclear region of cytoplasm
nucleus
apical plasma membrane
clathrin coat of coated pit
clathrin-coated vesicle membrane
Molecular Function
phosphatidylinositol binding
phosphatidylinositol-4,5-bisphosphate binding
integrin binding
clathrin binding
AP-2 adaptor complex binding
cargo receptor activity
low-density lipoprotein particle receptor binding
clathrin adaptor activity
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 768
Molecular Weight 82376.295
Theoretical pI 6.184
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID O88797
UniProtKB/Swiss-Prot Entry Name DAB2_RAT
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Lundby A, Secher A, Lage K, Nordsborg NB, Dmytriyev A, Lundby C, Olsen JV: Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues. Nat Commun. 2012 Jun 6;3:876. doi: 10.1038/ncomms1871. [PubMed:22673903 ]
  3. Tseng CP, Ely BD, Li Y, Pong RC, Hsieh JT: Regulation of rat DOC-2 gene during castration-induced rat ventral prostate degeneration and its growth inhibitory function in human prostatic carcinoma cells. Endocrinology. 1998 Aug;139(8):3542-53. doi: 10.1210/endo.139.8.6159. [PubMed:9681506 ]
  4. Wang Z, Tseng CP, Pong RC, Chen H, McConnell JD, Navone N, Hsieh JT: 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. 2002 Apr 12;277(15):12622-31. doi: 10.1074/jbc.M110568200. Epub 2002 Jan 25. [PubMed:11812785 ]
  5. Zhou J, Scholes J, Hsieh JT: Characterization of a novel negative regulator (DOC-2/DAB2) of c-Src in normal prostatic epithelium and cancer. J Biol Chem. 2003 Feb 28;278(9):6936-41. doi: 10.1074/jbc.M210628200. Epub 2002 Dec 8. [PubMed:12473651 ]
  6. Chetrit D, Barzilay L, Horn G, Bielik T, Smorodinsky NI, Ehrlich M: Negative regulation of the endocytic adaptor disabled-2 (Dab2) in mitosis. J Biol Chem. 2011 Feb 18;286(7):5392-403. doi: 10.1074/jbc.M110.161851. Epub 2010 Nov 19. [PubMed:21097498 ]
  7. Yu C, Feng W, Wei Z, Miyanoiri Y, Wen W, Zhao Y, Zhang M: Myosin VI undergoes cargo-mediated dimerization. Cell. 2009 Aug 7;138(3):537-48. doi: 10.1016/j.cell.2009.05.030. [PubMed:19665975 ]