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Identification
HMDB Protein ID HMDBP13782
Secondary Accession Numbers None
Name Disabled homolog 2-interacting protein
Synonyms
  1. DAB2 interaction protein
  2. DAB2-interacting protein
  3. ASK-interacting protein 1
  4. DOC-2/DAB-2 interactive protein
  5. AIP-1
Gene Name DAB2IP
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function Functions as a scaffold protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Involved in several processes such as innate immune response, inflammation and cell growth inhibition, apoptosis, cell survival, angiogenesis, cell migration and maturation. Plays also a role in cell cycle checkpoint control; reduces G1 phase cyclin levels resulting in G0/G1 cell cycle arrest. Mediates signal transduction by receptor-mediated inflammatory signals, such as the tumor necrosis factor (TNF), interferon (IFN) or lipopolysaccharide (LPS). Modulates the balance between phosphatidylinositol 3-kinase (PI3K)-AKT-mediated cell survival and apoptosis stimulated kinase (MAP3K5)-JNK signaling pathways; sequesters both AKT1 and MAP3K5 and counterbalances the activity of each kinase by modulating their phosphorylation status in response to proinflammatory stimuli. Acts as a regulator of the endoplasmic reticulum (ER) unfolded protein response (UPR) pathway; specifically involved in transduction of the ER stress-response to the JNK cascade through ERN1. Mediates TNF-alpha-induced apoptosis activation by facilitating dissociation of inhibitor 14-3-3 from MAP3K5; recruits the PP2A phosphatase complex which dephosphorylates MAP3K5 on 'Ser-966', leading to the dissociation of 13-3-3 proteins and activation of the MAP3K5-JNK signaling pathway in endothelial cells. Mediates also TNF/TRAF2-induced MAP3K5-JNK activation, while it inhibits CHUK-NF-kappa-B signaling. Acts a negative regulator in the IFN-gamma-mediated JAK-STAT signaling cascade by inhibiting smooth muscle cell (VSMCs) proliferation and intimal expansion, and thus, prevents graft arteriosclerosis (GA). Acts as a GTPase-activating protein (GAP) for the ADP ribosylation factor 6 (ARF6) and Ras. Promotes hydrolysis of the ARF6-bound GTP and thus, negatively regulates phosphatidylinositol 4,5-bisphosphate (PIP2)-dependent TLR4-TIRAP-MyD88 and NF-kappa-B signaling pathways in endothelial cells in response to lipopolysaccharides (LPS). Binds specifically to phosphatidylinositol 4-phosphate (PtdIns4P) and phosphatidylinositol 3-phosphate (PtdIns3P). In response to vascular endothelial growth factor (VEGFA), acts as a negative regulator of the VEGFR2-PI3K-mediated angiogenic signaling pathway by inhibiting endothelial cell migration and tube formation. In the developing brain, promotes both the transition from the multipolar to the bipolar stage and the radial migration of cortical neurons from the ventricular zone toward the superficial layer of the neocortex in a glial-dependent locomotion process. Probable downstream effector of the Reelin signaling pathway; promotes Purkinje cell (PC) dendrites development and formation of cerebellar synapses. Functions also as a tumor suppressor protein in prostate cancer progression; prevents cell proliferation and epithelial-to-mesenchymal transition (EMT) through activation of the glycogen synthase kinase-3 beta (GSK3B)-induced beta-catenin and inhibition of PI3K-AKT and Ras-MAPK survival downstream signaling cascades, respectively.
Pathways
  • Apoptosis
  • TNF signaling pathway
Reactions Not Available
GO Classification
Biological Process
cellular response to unfolded protein
cellular protein catabolic process
positive regulation of protein catabolic process
cell cycle
positive regulation of cell cycle arrest
positive regulation of apoptotic process
negative regulation of MAP kinase activity
I-kappaB phosphorylation
negative regulation of toll-like receptor 4 signaling pathway
negative regulation of fibroblast proliferation
negative regulation of I-kappaB kinase/NF-kappaB cascade
negative regulation of epithelial cell proliferation
inflammatory response
negative regulation of phosphatidylinositol 3-kinase cascade
cellular response to tumor necrosis factor
extrinsic apoptotic signaling pathway via death domain receptors
cellular response to vascular endothelial growth factor stimulus
positive regulation of neuron migration
activation of JUN kinase activity
cellular response to lipopolysaccharide
cellular response to interleukin-1
angiogenesis
positive regulation of dendrite development
negative regulation of GTPase activity
negative regulation of protein phosphorylation
intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
innate immune response
negative regulation of NF-kappaB transcription factor activity
negative regulation of transcription, DNA-dependent
positive regulation of neuron projection development
negative regulation of epidermal growth factor receptor signaling pathway
cellular response to epidermal growth factor stimulus
negative regulation of transcription from RNA polymerase II promoter
positive regulation of protein serine/threonine kinase activity
positive regulation of transcription from RNA polymerase II promoter
negative regulation of endothelial cell migration
MAPK cascade
negative regulation of canonical Wnt receptor signaling pathway
negative regulation of angiogenesis
activation of MAPKKK activity
cell motility involved in cerebral cortex radial glia guided migration
endothelial cell apoptotic process
layer formation in cerebral cortex
positive regulation of MAPK cascade
negative regulation of cellular protein catabolic process
negative regulation of epithelial cell migration
negative regulation of G0 to G1 transition
positive regulation of GTPase activity
negative regulation of phosphatidylinositol 3-kinase activity
negative regulation of protein serine/threonine kinase activity
negative regulation of vascular endothelial growth factor receptor signaling pathway
positive regulation of apoptotic signaling pathway
positive regulation of IRE1-mediated unfolded protein response
positive regulation of synapse maturation
reelin-mediated signaling pathway
regulation of GTPase activity
regulation of I-kappaB kinase/NF-kappaB signaling
regulation of p38MAPK cascade
regulation of protein-containing complex assembly
tube formation
vascular endothelial growth factor receptor-2 signaling pathway
negative regulation of Ras protein signal transduction
neuron projection morphogenesis
positive regulation of JNK cascade
positive regulation of JUN kinase activity
negative regulation of vascular endothelial growth factor signaling pathway
negative regulation of cell proliferation
negative regulation of ERK1 and ERK2 cascade
negative regulation of epithelial to mesenchymal transition
positive regulation of protein complex assembly
regulation of growth
positive regulation of proteasomal protein catabolic process
Cellular Component
cytosol
cytoplasm
plasma membrane
endocytic vesicle
dendrite
neuronal cell body
AIP1-IRE1 complex
cerebellar mossy fiber
climbing fiber
neuronal cell body membrane
parallel fiber
axon
Molecular Function
protein kinase binding
phosphatidylinositol-3-phosphate binding
phosphatidylinositol 3-kinase binding
protein-containing complex binding
GTPase activator activity
kinase binding
SH3 domain binding
phosphatidylinositol-4-phosphate binding
protein homodimerization activity
14-3-3 protein binding
cadherin binding
death receptor binding
mitogen-activated protein kinase kinase binding
vascular endothelial growth factor receptor 2 binding
signaling adaptor activity
mitogen-activated protein kinase kinase kinase binding
phosphatidylinositol 3-kinase regulatory subunit binding
identical protein binding
protein phosphatase 2A binding
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 1189
Molecular Weight 131623.86
Theoretical pI 8.721
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID Q5VWQ8
UniProtKB/Swiss-Prot Entry Name DAB2P_HUMAN
PDB IDs Not Available
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
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  13. Li X, Zhang R, Luo D, Park SJ, Wang Q, Kim Y, Min W: Tumor necrosis factor alpha-induced desumoylation and cytoplasmic translocation of homeodomain-interacting protein kinase 1 are critical for apoptosis signal-regulating kinase 1-JNK/p38 activation. J Biol Chem. 2005 Apr 15;280(15):15061-70. doi: 10.1074/jbc.M414262200. Epub 2005 Feb 8. [PubMed:15701637 ]
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  15. Min W, Lin Y, Tang S, Yu L, Zhang H, Wan T, Luhn T, Fu H, Chen H: AIP1 recruits phosphatase PP2A to ASK1 in tumor necrosis factor-induced ASK1-JNK activation. Circ Res. 2008 Apr 11;102(7):840-8. doi: 10.1161/CIRCRESAHA.107.168153. Epub 2008 Feb 21. [PubMed:18292600 ]
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