InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Dab2

Summary

InnateDB Protein

IDBP-128040.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Dab2

Protein Name

disabled homolog 2 (Drosophila)

Synonyms

5730435J12Rik; AA960054; AI957090; D15Wsu122e; D630005B22Rik; Doc-2; Doc2; p96;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000079689

InnateDB Gene

IDBG-128034 (Dab2)

Protein Structure

UniProt Annotation

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 containg 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. Isoform p96 is involved in endocytosis of megalin/LRP2 lipoprotein receptor during embryonal development. Required for recycling of the TGF-beta receptor. Isoform p67 is not involved in LDL receptor endocytosis. 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. Isoform p67 may be involved in transcriptional regulation. May act as a tumor suppressor. {ECO:0000269PubMed:11247302, ECO:0000269PubMed:11823414, ECO:0000269PubMed:11927540, ECO:0000269PubMed:12234931, ECO:0000269PubMed:12413896, ECO:0000269PubMed:15734730, ECO:0000269PubMed:15894542, ECO:0000269PubMed:16263760, ECO:0000269PubMed:16870701, ECO:0000269PubMed:16984970, ECO:0000269PubMed:19581931, ECO:0000269PubMed:20881059}.

Subcellular Localization

Cytoplasmic vesicle, clathrin-coated vesicle membrane. Membrane, clathrin-coated pit. Note=Colocalizes with large insert-containing isoforms of MYO6 at clathrin-coated pits/vesicles. During mitosis is progressively displaced from the membrane and translocated to the cytoplasm (By similarity). {ECO:0000250}.Isoform p96: Membrane, clathrin-coated pit. Note=Colocalizes with LDLR at clathrin-coated pits.Isoform p67: Cytoplasm {ECO:0000269PubMed:11104669}. Nucleus {ECO:0000269PubMed:11104669}. Note=Diffuse localization in the cytoplasm; does not localize to clathrin-coated pits.

Disease Associations

Tissue Specificity

Isoform p96 and isoform p67 are expressed in adult kidney and fibroblasts with isoform p96 being the predominant form. Isoform p67 is the predominant isoform expressed in embryonic visceral endoderm. {ECO:0000269PubMed:16263760}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 50 experimentally validated interaction(s) in this database.
They are also associated with 64 interaction(s) predicted by orthology.

Experimentally validated
Total	50 [view]
Protein-Protein	48 [view]
Protein-DNA	2 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	64 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005178	integrin binding
GO:0005515	protein binding
GO:0005546	phosphatidylinositol-4,5-bisphosphate binding
GO:0008022	protein C-terminus binding
GO:0030276	clathrin binding
GO:0035091	phosphatidylinositol binding
GO:0035612	AP-2 adaptor complex binding
GO:0035615	clathrin adaptor activity
GO:0038024	cargo receptor activity
GO:0046332	SMAD binding

Biological Process

GO:0000904	cell morphogenesis involved in differentiation
GO:0001701	in utero embryonic development
GO:0001921	positive regulation of receptor recycling
GO:0001934	positive regulation of protein phosphorylation
GO:0006898	receptor-mediated endocytosis
GO:0006907	pinocytosis
GO:0006915	apoptotic process
GO:0007257	activation of JUN kinase activity
GO:0007492	endoderm development
GO:0007588	excretion
GO:0010718	positive regulation of epithelial to mesenchymal transition
GO:0010862	positive regulation of pathway-restricted SMAD protein phosphorylation
GO:0015031	protein transport
GO:0016055	Wnt signaling pathway
GO:0030099	myeloid cell differentiation
GO:0030335	positive regulation of cell migration
GO:0030511	positive regulation of transforming growth factor beta receptor signaling pathway
GO:0032091	negative regulation of protein binding
GO:0032436	positive regulation of proteasomal ubiquitin-dependent protein catabolic process
GO:0032968	positive regulation of transcription elongation from RNA polymerase II promoter
GO:0043066	negative regulation of apoptotic process
GO:0045785	positive regulation of cell adhesion
GO:0045807	positive regulation of endocytosis
GO:0045892	negative regulation of transcription, DNA-templated
GO:0045893	positive regulation of transcription, DNA-templated
GO:0048268	clathrin coat assembly
GO:0060391	positive regulation of SMAD protein import into nucleus
GO:0060766	negative regulation of androgen receptor signaling pathway
GO:0071560	cellular response to transforming growth factor beta stimulus
GO:0090090	negative regulation of canonical Wnt signaling pathway
GO:1900026	positive regulation of substrate adhesion-dependent cell spreading
GO:2000096	positive regulation of Wnt receptor signaling pathway, planar cell polarity pathway
GO:2000370	positive regulation of clathrin-mediated endocytosis
GO:2000643	positive regulation of early endosome to late endosome transport
GO:2001046	positive regulation of integrin-mediated signaling pathway
GO:2001237	negative regulation of extrinsic apoptotic signaling pathway

Cellular Component

GO:0005634	nucleus
GO:0005730	nucleolus
GO:0005737	cytoplasm
GO:0005886	plasma membrane
GO:0005905	coated pit
GO:0016324	apical plasma membrane
GO:0030132	clathrin coat of coated pit
GO:0030665	clathrin-coated vesicle membrane
GO:0043231	intracellular membrane-bounded organelle
GO:0070022	transforming growth factor beta receptor homodimeric complex
GO:0070062	extracellular vesicular exosome