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FLASH GENE

Symbol

DAB2IP

contributors: mct/pgu - updated : 13-02-2010

HGNC name	DAB2 interacting protein
HGNC id	17294

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N-terminus containing the C2 and GAP domains constitutively binds to MAP3K5 and facilitating the release of 14-3-3 from MAP3K5
	one PH domain and one FLR motif
	a proline-rich region (amino acids 796-807) critical for maintaining DAB2IP in a closed form, which associates with a region of TNFR1 distinct from the death domain, the site of TNFR1 association with TRADD
	C terminal leucine zipper domain

HOMOLOGY

interspecies

homolog to rattus Dip1/2

intraspecies

homolog to RASA1

Homologene

FAMILY

RAS GTPase activating protein family

CATEGORY

regulatory , tumor suppressor

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,mitochondria
	intracellular,cytoplasm,organelle,membrane
	intracellular,nucleus

basic FUNCTION	mediating TNF-alpha-induced ASK1 activation by facilitating dissociation of inhibitor 14-3-3 from MAP3K5, a novel mechanism by which TNF-alpha activates MAP3K5
	transducer in TNF-induced TRAF2-dependent activation of MAP3K5 that mediates a balance between JNK versus NF-kappaB signaling
	being essential for transducing the IRE1-mediated ER stress response
	potent growth inhibitor by inducing G0/G1 cell cycle arrest and is proapoptotic in response to stress
	can coordinate PI3K-Akt inactivation with ASK1 activation pathways
	unique scaffold protein to balance pathways of cell proliferation, survival, and death
	functions as a scaffold protein in regulating epithelial-to-mesenchymal transition by modulating nuclear beta-catenin/T-cell factor activity
	; suppress cell survival and proliferation through suppression of the PI3K-Act and RAS pathways and to induce apoptosis through activation of MAP3K5, a member of the JNK and MAPK14 pathways
	endogenous inhibitor of KDR-mediated signaling, an important regulator of angiogenesis control (
	GTPase activating protein that binds to Disabled-1, a cytosolic adapter protein involved in Reelin signaling and brain development
	plays an important role in dendrite development and regulates the number of synapses in the cerebellum

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	DAB2
	MAP3K5

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   in prostate cancer tumoral fusion translocation     fused with MLL in t(9;11) (q34;q23) in acute myeloid leukemia tumoral         leads to imbalance of cell survival and apoptosis pathways, which plays a significant role in tumor development

Susceptibility

to aggressive prostate cancer to early onset myocardial infarction, peripheral arterial disease, abdominal aortic aneurysms and pulmonary embolism

Variant & Polymorphism SNP	in the DAB2IP gene is associated with risk of aggressive prostate cancer (PCa), and loss of DAB2IP expression is frequently detected in metastatic PCa
	rs7025486[A] is associated with early onset myocardial infarction, peripheral arterial disease, abdominal aortic aneurysms and pulmonary embolism

Candidate gene
Marker	assessment of DAB2IP may provide a prognostic biomarker in prostate carcinoma metastasis
Therapy target
	System Type Disorder Pubmed cancer metastases   potential therapeutic target for Prostate Carcinoma metastasis

ANIMAL & CELL MODELS

	AIP1-deficient mice (AIP1-KO)
	Dab2IP knock-down mice did not exhibit severe ataxia or cerebellar hypoplasia, but Dab2IP deficiency produced a number of cerebellar abnormalities such as a delay in the development of Purkinje cell (PC) dendrites