Summary

Name DAB2IP
Full Name Disabled homolog 2-interacting protein
Synonyms DAB2 interaction protein, DAB2-interacting protein, ASK-interacting protein 1, AIP-1, DOC-2/DAB-2 interactive protein | AF9Q34, AIP1, KIAA1743
Primary ID Q5VWQ8
Links - -
Type protein
Relations 29
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.

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Modifications Tables

Relations

Regulator Mechanism target score
+ up-regulates activity img/direct-activation.png phosphorylation DAB2IP 0.439
Publications: 2 Organism: Homo Sapiens, Bos Taurus
+ down-regulates activity img/direct_inhibition.png phosphorylation DAB2IP 0.516
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png binding PIK3CA 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding GATA1 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding ERN1 0.376
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination DAB2IP 0.332
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png gtpase-activating protein KRAS 0.493
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/indirect_inhibition.png HIF1A 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by repression img/indirect_inhibition.png transcriptional regulation KIT 0.279
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination DAB2IP 0.273
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity img/direct_inhibition.png relocalization CTNNB1 0.304
Publications: 1 Organism: Mus Musculus
+ down-regulates img/indirect_inhibition.png Survival 0.7
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination DAB2IP 0.266
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png binding AR 0.338
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png binding AKT 0.516
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png binding PIK3R1 0.285
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/indirect_inhibition.png Cell_migration 0.7
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by repression img/indirect_inhibition.png transcriptional regulation ZEB1 0.273
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png gtpase-activating protein NRAS 0.468
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding MAP3K5 0.834
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding PP2Ca_R1A_Bd 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png binding STAT3 0.358
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by repression img/indirect_inhibition.png transcriptional regulation PROX1 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png gtpase-activating protein HRAS 0.578
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png binding 14-3-3 0.302
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png binding JAK2 0.36
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding DAB2IP 0.542
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding GSK3B 0.314
Publications: 1 Organism: Homo Sapiens