DegronMD - Q5VWQ8(DAB2IP)

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 pro-inflammatory 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. {ECO:0000269|PubMed:12813029, ECO:0000269|PubMed:17389591, ECO:0000269|PubMed:18292600, ECO:0000269|PubMed:19033661, ECO:0000269|PubMed:19903888, ECO:0000269|PubMed:19948740, ECO:0000269|PubMed:20080667, ECO:0000269|PubMed:20154697, ECO:0000269|PubMed:21700930, ECO:0000269|PubMed:22696229}. View more >>

GO - Biological processes (BP): angiogenesis [GO:0001525]; cell cycle [GO:0007049]; cell motility involved in cerebral cortex radial glia guided migration [GO:0021814]; cellular protein catabolic process [GO:0044257]; cellular response to epidermal growth factor stimulus [GO:0071364]; cellular response to interleukin-1 [GO:0071347]; cellular response to lipopolysaccharide [GO:0071222]; cellular response to tumor necrosis factor [GO:0071356]; cellular response to unfolded protein [GO:0034620]; cellular response to vascular endothelial growth factor stimulus [GO:0035924]; endothelial cell apoptotic process [GO:0072577]; extrinsic apoptotic signaling pathway via death domain receptors [GO:0008625]; I-kappaB phosphorylation [GO:0007252]; inflammatory response [GO:0006954]; innate immune response [GO:0045087]; intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress [GO:0070059]; layer formation in cerebral cortex [GO:0021819]; negative regulation of angiogenesis [GO:0016525]; negative regulation of canonical Wnt signaling pathway [GO:0090090]; negative regulation of cell population proliferation [GO:0008285]; negative regulation of cellular protein catabolic process [GO:1903363]; negative regulation of endothelial cell migration [GO:0010596]; negative regulation of epidermal growth factor receptor signaling pathway [GO:0042059]; negative regulation of epithelial cell migration [GO:0010633]; negative regulation of epithelial cell proliferation [GO:0050680]; negative regulation of epithelial to mesenchymal transition [GO:0010719]; negative regulation of ERK1 and ERK2 cascade [GO:0070373]; negative regulation of fibroblast proliferation [GO:0048147]; negative regulation of G0 to G1 transition [GO:0070317]; negative regulation of GTPase activity [GO:0034260]; negative regulation of I-kappaB kinase/NF-kappaB signaling [GO:0043124]; negative regulation of MAP kinase activity [GO:0043407]; negative regulation of NF-kappaB transcription factor activity [GO:0032088]; negative regulation of phosphatidylinositol 3-kinase activity [GO:0043553]; negative regulation of phosphatidylinositol 3-kinase signaling [GO:0014067]; negative regulation of protein phosphorylation [GO:0001933]; negative regulation of protein serine/threonine kinase activity [GO:0071901]; negative regulation of Ras protein signal transduction [GO:0046580]; negative regulation of toll-like receptor 4 signaling pathway [GO:0034144]; negative regulation of transcription, DNA-templated [GO:0045892]; negative regulation of transcription by RNA polymerase II [GO:0000122]; negative regulation of vascular endothelial growth factor receptor signaling pathway [GO:0030948]; negative regulation of vascular endothelial growth factor signaling pathway [GO:1900747]; neuron projection morphogenesis [GO:0048812]; positive regulation of apoptotic process [GO:0043065]; positive regulation of apoptotic signaling pathway [GO:2001235]; positive regulation of dendrite development [GO:1900006]; positive regulation of IRE1-mediated unfolded protein response [GO:1903896]; positive regulation of JNK cascade [GO:0046330]; positive regulation of JUN kinase activity [GO:0043507]; positive regulation of MAPK cascade [GO:0043410]; positive regulation of neuron migration [GO:2001224]; positive regulation of neuron projection development [GO:0010976]; positive regulation of proteasomal protein catabolic process [GO:1901800]; positive regulation of protein catabolic process [GO:0045732]; positive regulation of protein-containing complex assembly [GO:0031334]; positive regulation of protein serine/threonine kinase activity [GO:0071902]; positive regulation of synapse maturation [GO:0090129]; positive regulation of transcription by RNA polymerase II [GO:0045944]; reelin-mediated signaling pathway [GO:0038026]; regulation of cell cycle [GO:0051726]; regulation of growth [GO:0040008]; regulation of GTPase activity [GO:0043087]; regulation of I-kappaB kinase/NF-kappaB signaling [GO:0043122]; regulation of p38MAPK cascade [GO:1900744]; regulation of protein-containing complex assembly [GO:0043254]; tube formation [GO:0035148]; vascular endothelial growth factor receptor-2 signaling pathway [GO:0036324] View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.R727H	TCGA-A5-A1OF	UCEC	TCGA	ARSSS	DEG_SPOP_SBC_1	724:728	Mutation altering degron motif	0.8244
p.R727H	DO42568	UCEC	ICGC	ARSSS	DEG_SPOP_SBC_1	724:728	Mutation altering degron motif	0.8244
p.A808V	TCGA-A5-A1OF	UCEC	TCGA	PTTPGTS	DEG_SCF_FBW7_1	807:813	Mutation altering degron motif	0.6936
p.A808V	DO42568	UCEC	ICGC	PTTPGTS	DEG_SCF_FBW7_1	807:813	Mutation altering degron motif	0.6936
p.D820N	TCGA-AP-A1DV	UCEC	TCGA	PTTPGTS	DEG_SCF_FBW7_1	807:813	Mutation rewiring degron network	0.1389
p.D820N	DO43186	UCEC	ICGC	PTTPGTS	DEG_SCF_FBW7_1	807:813	Mutation rewiring degron network	0.1389
p.S799C	TCGA-CC-A3M9	LIHC	TCGA	PTTPGTS	DEG_SCF_FBW7_1	807:813	Mutation blocking phosphorylation signal	0.5556
p.S799C	DO44946	LIHC	ICGC	PTTPGTS	DEG_SCF_FBW7_1	807:813	Mutation blocking phosphorylation signal	0.5556
p.Q806H	TCGA-D6-A6ES	HNSC	TCGA	PTTPGTS	DEG_SCF_FBW7_1	807:813	Mutation rewiring degron network	0.3056
p.Q806H	DO52086	HNSC	ICGC	PTTPGTS	DEG_SCF_FBW7_1	807:813	Mutation rewiring degron network	0.3056
p.R727C	TCGA-D7-A6EY	STAD	TCGA	ARSSS	DEG_SPOP_SBC_1	724:728	Mutation altering degron motif	0.8301
p.R727C	DO50118	STAD	ICGC	ARSSS	DEG_SPOP_SBC_1	724:728	Mutation altering degron motif	0.8301
p.P797Q	TCGA-DA-A1IA	SKCM	TCGA	PTTPGTS	DEG_SCF_FBW7_1	807:813	Mutation rewiring degron network	0.0556
p.P797Q	DO38022	SKCM	ICGC	PTTPGTS	DEG_SCF_FBW7_1	807:813	Mutation rewiring degron network	0.0556
p.G738S	TCGA-EE-A20C	SKCM	TCGA	ARSSS	DEG_SPOP_SBC_1	724:728	Mutation rewiring degron network	0.0556
p.G738S	DO222775	MELA	ICGC	ARSSS	DEG_SPOP_SBC_1	724:728	Mutation rewiring degron network	0.0556
p.G738S	DO47665	SKCM	ICGC	ARSSS	DEG_SPOP_SBC_1	724:728	Mutation rewiring degron network	0.0556
p.S799A	TCGA-G3-A5SJ	LIHC	TCGA	PTTPGTS	DEG_SCF_FBW7_1	807:813	Mutation blocking phosphorylation signal	0.5556
p.S799A	DO44938	LIHC	ICGC	PTTPGTS	DEG_SCF_FBW7_1	807:813	Mutation blocking phosphorylation signal	0.5556
p.R816C	TCGA-XF-AAN7	BLCA	TCGA	PTTPGTS	DEG_SCF_FBW7_1	807:813	Mutation rewiring degron network	0.25
p.R816C	DO51946	BLCA	ICGC	PTTPGTS	DEG_SCF_FBW7_1	807:813	Mutation rewiring degron network	0.25
p.R727L	DO228971	LICA	ICGC	ARSSS	DEG_SPOP_SBC_1	724:728	Mutation altering degron motif	0.8428
p.P815S	DO228349	MALY	ICGC	PTTPGTS	DEG_SCF_FBW7_1	807:813	Mutation rewiring degron network	0.2778
p.A737T	DO229253	THCA	ICGC	ARSSS	DEG_SPOP_SBC_1	724:728	Mutation rewiring degron network	0.0833
p.G817V	SIDM01146	Gastric Carcinoma	GDSC	PTTPGTS	DEG_SCF_FBW7_1	807:813	Mutation rewiring degron network	0.2222
p.G817V	NCI-SNU-1	stomach	COSMIC	PTTPGTS	DEG_SCF_FBW7_1	807:813	Mutation rewiring degron network	0.2222
p.S814L	SIDM00560	Gastric Carcinoma	GDSC	PTTPGTS	DEG_SCF_FBW7_1	807:813	Mutation rewiring degron network	0.3056
p.A806V	ACH-000887	Brain Cancer	CCLE	PTTPGTS	DEG_SCF_FBW7_1	807:813	Mutation rewiring degron network	0.3056
p.G721V	ACH-000932	Gastric Cancer	CCLE	ARSSS	DEG_SPOP_SBC_1	724:728	Mutation rewiring degron network	0.25
p.G721V	NCI-SNU-1	stomach	COSMIC	ARSSS	DEG_SPOP_SBC_1	724:728	Mutation rewiring degron network	0.25
p.R823I	ACH-001498	Lymphoma	CCLE	PTTPGTS	DEG_SCF_FBW7_1	807:813	Mutation rewiring degron network	0.0556
p.H730Y	ACH-001738	Leukemia	CCLE	ARSSS	DEG_SPOP_SBC_1	724:728	Mutation rewiring degron network	0.2778
p.H730Y	CCRF-CEM	haematopoietic and lymphoid tissue	COSMIC	ARSSS	DEG_SPOP_SBC_1	724:728	Mutation rewiring degron network	0.2778
p.R819W	P30-OHK	haematopoietic and lymphoid tissue	COSMIC	PTTPGTS	DEG_SCF_FBW7_1	807:813	Mutation rewiring degron network	0.1667
p.A816V	NB5	autonomic ganglia	COSMIC	PTTPGTS	DEG_SCF_FBW7_1	807:813	Mutation rewiring degron network	0.25
p.A816V	CAL-54	kidney	COSMIC	PTTPGTS	DEG_SCF_FBW7_1	807:813	Mutation rewiring degron network	0.25

DegronMD: protein-targeted degradation, mutation and drug response to degrons

DAB2IP

UniProt ID: Q5VWQ8

Entrez ID: 153090

Protein name: Disabled homolog 2-interacting protein (DAB2 interaction protein) (DAB2-interacting protein) (ASK-interacting protein 1) (AIP-1) (DOC-2/DAB-2 interactive protein)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for DAB2IP in