DAB2IP (DAB2 interacting protein)

Gene

• Entrez ID: 153090
• Gene name: DAB2 interacting protein
• Gene symbol: DAB2IP
• Synonyms: AF9Q34, AIP-1, AIP1, DIP1/2
• Chromosome: 9
• Chromosome location: 9q33.2
• Summary: DAB2IP is a Ras (MIM 190020) GTPase-activating protein (GAP) that acts as a tumor suppressor. The DAB2IP gene is inactivated by methylation in prostate and breast cancers (Yano et al., 2005 [PubMed 15386433]).[supplied by OMIM, May 2010]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT003041	hsa-miR-338-3p	qRT-PCR, Western blot	18684991
MIRT040771	hsa-miR-18a-3p	CLASH	23622248
MIRT052296	hsa-let-7b-5p	CLASH	23622248
MIRT173868	hsa-miR-32-5p	HITS-CLIP	22473208
MIRT173869	hsa-miR-92a-3p	HITS-CLIP	22473208
MIRT173873	hsa-miR-92b-3p	HITS-CLIP	22473208
MIRT173873	hsa-miR-92b-3p	Luciferase reporter assay, qRT-PCR, Western blot	27430302
MIRT736191	hsa-miR-1229-5p	PAR-CLIP	26701625
MIRT737148	hsa-miR-1293	PAR-CLIP	26701625
MIRT738693	hsa-miR-197-5p	PAR-CLIP	26701625
MIRT740088	hsa-miR-3132	PAR-CLIP	26701625
MIRT740210	hsa-miR-3144-5p	PAR-CLIP	26701625
MIRT740978	hsa-miR-3191-3p	PAR-CLIP	26701625
MIRT741048	hsa-miR-3194-3p	PAR-CLIP	26701625
MIRT741269	hsa-miR-326	PAR-CLIP	26701625
MIRT741327	hsa-miR-330-5p	PAR-CLIP	26701625
MIRT741825	hsa-miR-363-5p	PAR-CLIP	26701625
MIRT742816	hsa-miR-3907	PAR-CLIP	26701625
MIRT743393	hsa-miR-4257	PAR-CLIP	26701625
MIRT745145	hsa-miR-4483	PAR-CLIP	26701625
MIRT746540	hsa-miR-4651	PAR-CLIP	26701625
MIRT746592	hsa-miR-4652-5p	PAR-CLIP	26701625
MIRT746796	hsa-miR-4667-5p	PAR-CLIP	26701625
MIRT747273	hsa-miR-4700-5p	PAR-CLIP	26701625
MIRT751208	hsa-miR-5691	PAR-CLIP	26701625
MIRT751977	hsa-miR-608	PAR-CLIP	26701625
MIRT752684	hsa-miR-637	PAR-CLIP	26701625
MIRT754062	hsa-miR-6732-5p	PAR-CLIP	26701625
MIRT754453	hsa-miR-6745	PAR-CLIP	26701625
MIRT754546	hsa-miR-6748-5p	PAR-CLIP	26701625
MIRT754625	hsa-miR-6752-5p	PAR-CLIP	26701625
MIRT754785	hsa-miR-6756-5p	PAR-CLIP	26701625
MIRT755093	hsa-miR-6766-5p	PAR-CLIP	26701625
MIRT755180	hsa-miR-6769a-5p	PAR-CLIP	26701625
MIRT755226	hsa-miR-6769b-5p	PAR-CLIP	26701625
MIRT756459	hsa-miR-6805-3p	PAR-CLIP	26701625
MIRT756650	hsa-miR-6810-5p	PAR-CLIP	26701625
MIRT757359	hsa-miR-6842-5p	PAR-CLIP	26701625
MIRT757463	hsa-miR-6847-5p	PAR-CLIP	26701625
MIRT758985	hsa-miR-7110-5p	PAR-CLIP	26701625
MIRT759255	hsa-miR-7155-5p	PAR-CLIP	26701625
MIRT760055	hsa-miR-8065	PAR-CLIP	26701625
MIRT760265	hsa-miR-8089	PAR-CLIP	26701625

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	IDA	15310755
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	IMP	20154697
GO:0000165	Process	MAPK cascade	TAS
GO:0000185	Process	Activation of MAPKKK activity	IDA	19903888
GO:0001525	Process	Angiogenesis	IEA
GO:0001933	Process	Negative regulation of protein phosphorylation	IMP	20080667
GO:0001933	Process	Negative regulation of protein phosphorylation	ISS
GO:0005096	Function	GTPase activator activity	IEA
GO:0005123	Function	Death receptor binding	IPI	15310755
GO:0005515	Function	Protein binding	IPI	12813029, 17389591, 19903888, 20080667
GO:0005737	Component	Cytoplasm	IDA	15310755, 19948740
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	IDA	15310755, 19948740
GO:0006954	Process	Inflammatory response	IEA
GO:0007049	Process	Cell cycle	IEA
GO:0007252	Process	I-kappaB phosphorylation	ISS
GO:0007257	Process	Activation of JUN kinase activity	IDA	12813029
GO:0008285	Process	Negative regulation of cell population proliferation	IDA	19903888
GO:0008625	Process	Extrinsic apoptotic signaling pathway via death domain receptors	IMP	19903888
GO:0010596	Process	Negative regulation of endothelial cell migration	IMP	19033661
GO:0010633	Process	Negative regulation of epithelial cell migration	IMP	20080667
GO:0010633	Process	Negative regulation of epithelial cell migration	TAS	20080667
GO:0010719	Process	Negative regulation of epithelial to mesenchymal transition	IDA	20154697
GO:0010719	Process	Negative regulation of epithelial to mesenchymal transition	IMP	20080667
GO:0010976	Process	Positive regulation of neuron projection development	ISS
GO:0014067	Process	Negative regulation of phosphatidylinositol 3-kinase signaling	IDA	19903888
GO:0016525	Process	Negative regulation of angiogenesis	IDA	19033661
GO:0017124	Function	SH3 domain binding	IDA	19033661, 19903888
GO:0019900	Function	Kinase binding	IPI	17389591
GO:0019901	Function	Protein kinase binding	IDA	18281285
GO:0019901	Function	Protein kinase binding	IPI	20080667
GO:0021814	Process	Cell motility involved in cerebral cortex radial glia guided migration	ISS
GO:0021819	Process	Layer formation in cerebral cortex	ISS
GO:0030139	Component	Endocytic vesicle	IDA	19948740
GO:0030424	Component	Axon	ISS
GO:0030425	Component	Dendrite	IEA
GO:0030948	Process	Negative regulation of vascular endothelial growth factor receptor signaling pathway	IMP	19033661
GO:0031334	Process	Positive regulation of protein-containing complex assembly	IDA	18281285
GO:0031434	Function	Mitogen-activated protein kinase kinase binding	IPI	17389591
GO:0031435	Function	Mitogen-activated protein kinase kinase kinase binding	IPI	12813029
GO:0032088	Process	Negative regulation of NF-kappaB transcription factor activity	IMP	20154697
GO:0032266	Function	Phosphatidylinositol-3-phosphate binding	IDA	19948740
GO:0032809	Component	Neuronal cell body membrane	ISS
GO:0034144	Process	Negative regulation of toll-like receptor 4 signaling pathway	IDA	19948740
GO:0034260	Process	Negative regulation of GTPase activity	IMP	20154697
GO:0034260	Process	Negative regulation of GTPase activity	ISS
GO:0034620	Process	Cellular response to unfolded protein	TAS	22013210
GO:0035148	Process	Tube formation	IMP	19033661
GO:0035591	Function	Signaling adaptor activity	IDA	20080667
GO:0035662	Function	Toll-like receptor 4 binding	IDA	19948740
GO:0035924	Process	Cellular response to vascular endothelial growth factor stimulus	IDA	19033661
GO:0035924	Process	Cellular response to vascular endothelial growth factor stimulus	ISS
GO:0036312	Function	Phosphatidylinositol 3-kinase regulatory subunit binding	IDA	19903888
GO:0036324	Process	Vascular endothelial growth factor receptor-2 signaling pathway	ISS
GO:0038026	Process	Reelin-mediated signaling pathway	IEA
GO:0040008	Process	Regulation of growth	IEA
GO:0042059	Process	Negative regulation of epidermal growth factor receptor signaling pathway	ISS	11812785
GO:0042802	Function	Identical protein binding	IPI	12813029
GO:0042803	Function	Protein homodimerization activity	IPI	12813029
GO:0043025	Component	Neuronal cell body	ISS
GO:0043065	Process	Positive regulation of apoptotic process	IDA	17389591, 19903888
GO:0043087	Process	Regulation of GTPase activity	ISS
GO:0043122	Process	Regulation of I-kappaB kinase/NF-kappaB signaling	ISS
GO:0043124	Process	Negative regulation of I-kappaB kinase/NF-kappaB signaling	IDA	15310755, 17389591
GO:0043184	Function	Vascular endothelial growth factor receptor 2 binding	IPI	19033661
GO:0043254	Process	Regulation of protein-containing complex assembly	IDA	19948740
GO:0043407	Process	Negative regulation of MAP kinase activity	IDA	12813029
GO:0043407	Process	Negative regulation of MAP kinase activity	IMP	20154697
GO:0043410	Process	Positive regulation of MAPK cascade	IDA	19903888
GO:0043507	Process	Positive regulation of JUN kinase activity	IDA	15310755
GO:0043547	Process	Positive regulation of GTPase activity	IEA
GO:0043548	Function	Phosphatidylinositol 3-kinase binding	IDA	19033661
GO:0043553	Process	Negative regulation of phosphatidylinositol 3-kinase activity	IDA	19903888
GO:0044257	Process	Cellular protein catabolic process	IDA	17389591
GO:0044300	Component	Cerebellar mossy fiber	ISS
GO:0044301	Component	Climbing fiber	ISS
GO:0044877	Function	Protein-containing complex binding	IDA	19903888
GO:0045087	Process	Innate immune response	IEA
GO:0045296	Function	Cadherin binding	HDA	25468996
GO:0045732	Process	Positive regulation of protein catabolic process	ISS
GO:0045892	Process	Negative regulation of transcription, DNA-templated	IMP	20080667
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	15310755, 17389591
GO:0046330	Process	Positive regulation of JNK cascade	IDA	17389591, 19903888
GO:0046580	Process	Negative regulation of Ras protein signal transduction	IC	20154697
GO:0048147	Process	Negative regulation of fibroblast proliferation	ISS
GO:0048812	Process	Neuron projection morphogenesis	ISS
GO:0050680	Process	Negative regulation of epithelial cell proliferation	IMP	20154697
GO:0051721	Function	Protein phosphatase 2A binding	IDA	20080667
GO:0070059	Process	Intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	ISS	18281285
GO:0070273	Function	Phosphatidylinositol-4-phosphate binding	IDA	19948740
GO:0070317	Process	Negative regulation of G0 to G1 transition	IDA	19903888
GO:0070373	Process	Negative regulation of ERK1 and ERK2 cascade	IDA	19903888
GO:0071158	Process	Positive regulation of cell cycle arrest	IDA	19903888
GO:0071222	Process	Cellular response to lipopolysaccharide	IDA	19948740
GO:0071347	Process	Cellular response to interleukin-1	IDA	19948740
GO:0071356	Process	Cellular response to tumor necrosis factor	IDA	12813029, 15310755, 17389591
GO:0071364	Process	Cellular response to epidermal growth factor stimulus	ISS	11812785
GO:0071889	Function	14-3-3 protein binding	IDA	17389591
GO:0071901	Process	Negative regulation of protein serine/threonine kinase activity	IDA	19903888
GO:0071901	Process	Negative regulation of protein serine/threonine kinase activity	IMP	20154697
GO:0071902	Process	Positive regulation of protein serine/threonine kinase activity	IDA	19903888
GO:0071902	Process	Positive regulation of protein serine/threonine kinase activity	IMP	20080667
GO:0072577	Process	Endothelial cell apoptotic process	TAS	19903888
GO:0090090	Process	Negative regulation of canonical Wnt signaling pathway	IMP	20080667
GO:0090090	Process	Negative regulation of canonical Wnt signaling pathway	ISS
GO:0090129	Process	Positive regulation of synapse maturation	ISS
GO:1900006	Process	Positive regulation of dendrite development	ISS
GO:1900744	Process	Regulation of p38MAPK cascade	ISS
GO:1900747	Process	Negative regulation of vascular endothelial growth factor signaling pathway	ISS
GO:1901800	Process	Positive regulation of proteasomal protein catabolic process	IMP	20080667
GO:1903363	Process	Negative regulation of cellular protein catabolic process	IDA	19903888
GO:1903896	Process	Positive regulation of IRE1-mediated unfolded protein response	TAS	22013210
GO:1990032	Component	Parallel fiber	ISS
GO:1990597	Component	AIP1-IRE1 complex	IDA	18281285
GO:2001224	Process	Positive regulation of neuron migration	ISS
GO:2001235	Process	Positive regulation of apoptotic signaling pathway	IDA	19903888

Other IDs

• MIM: 609205
• HGNC: 17294
• e!Ensembl: ENSG00000136848

Protein

• UniProt ID: Q5VWQ8
• 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)
• Protein 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.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00168	C2	213 → 313	C2 domain	Domain
  PF00616	RasGAP	392 → 470	GTPase-activator protein for Ras-like GTPase	Family
  PF00616	RasGAP	460 → 563	GTPase-activator protein for Ras-like GTPase	Family
  PF12004	DUF3498	646 → 1159	Domain of unknown function (DUF3498)	Family

• Sequence:

  MSAGGSARKSTGRSSYYYRLLRRPRLQRQRSRSRSRTRPARESPQERPGSRRSLPGSLSE
  KSPSMEPSAATPFRVTGFLSRRLKGSIKRTKSQPKLDRNHSFRHILPGFRSAAAAAADNE
  RSHLMPRLKESRSHESLLSPSSAVEALDLSMEEEVVIKPVHSSILGQDYCFEVTTSSGSK
  CFSCRSAAERDKWMENLRRAVHPNKDNSRRVEHILKLWVIEAKDLPAKKKYLCELCLDDV
  LYARTTGKLKTDNVFWGEHFEFHNLPPLRTVTVHLYRETDKKKKKERNSYLGLVSLPAAS
  VAGRQFVEKWYPVVTPNPKGGKGPGPMIRIKARYQTITILPMEMYKEFAEHITNHYLGLC
  AALEPILSAKTKEEMASALVHILQSTGKVKDFLTDLMMSEVDRCGDNEHLIFRENTLATK
  AIEEYLKLVGQKYLQDALGEFIKALYESDENCEVDPSKCSAADLPEHQGNLKMCCELAFC
  KIINSYCVFPRELKEVFASWRQECSSRGRPDISERLISASLFLRFLCPAIMSPSLFNLLQ
  EYPDDRTARTLTLIAKVTQNLANFAKFGSKEEYMSFMNQFLEHEWTNMQRFLLEISNPET
  LSNTAGFEGYIDLGRELSSLHSLLWEAVSQLEQSIVSKLGPLPRILRDVHTALSTPGSGQ
  LPGTNDLASTPGSGSSSISAGLQKMVIENDLSGLIDFTRLPSPTPENKDLFFVTRSSGVQ
  PSPARSSSYSEANEPDLQMANGGKSLSMVDLQDARTLDGEAGSPAGPDVLPTDGQAAAAQ
  LVAGWPARATPVNLAGLATVRRAGQTPTTPGTSEGAPGRPQLLAPLSFQNPVYQMAAGLP
  LSPRGLGDSGSEGHSSLSSHSNSEELAAAAKLGSFSTAAEELARRPGELARRQMSLTEKG
  GQPTVPRQNSAGPQRRIDQPPPPPPPPPPAPRGRTPPNLLSTLQYPRPSSGTLASASPDW
  VGPSTRLRQQSSSSKGDSPELKPRAVHKQGPSPVSPNALDRTAAWLLTMNAQLLEDEGLG
  PDPPHRDRLRSKDELSQAEKDLAVLQDKLRISTKKLEEYETLFKCQEETTQKLVLEYQAR
  LEEGEERLRRQQEDKDIQMKGIISRLMSVEEELKKDHAEMQAAVDSKQKIIDAQEKRIAS
  LDAANARLMSALTQLKERYSMQARNGISPTNPTKLQITENGEFRNSSNC

• Sequence length: 1189

Pathways

KEGG:

Apoptosis
TNF signaling pathway

Reactome:

Regulation of RAS by GAPs

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Coronary artery disease	Coronary Artery Disease	rs137852988, rs121918313, rs-1, rs121918529, rs121918531, rs137852340, rs405509, rs1555800701, rs1215189537	29212778
Prostate cancer	Malignant neoplasm of prostate	rs121909139, rs121909140, rs121909141, rs121909142, rs121909143, rs606231169, rs606231170, rs137852584, rs137852578, rs137852580, rs137852581, rs137852582	18073375
Myocardial infarction	Myocardial Infarction	rs12316150, rs41303970, rs909253, rs7291467, rs2234693	20622881
Lung cancer	Malignant neoplasm of lung	rs121913530, rs121913529, rs878855122, rs1057519784, rs770315135	22046421
Aortic aneurysm	Aortic Aneurysm, Abdominal	rs1555554098, rs267606902, rs121434526, rs121434527, rs121434528, rs387906592, rs387906781, rs387906782, rs397516685, rs397514037, rs112901682, rs397515325, rs397515330, rs794728025, rs112602953, rs794728021, rs8046180, rs797045725, rs876657852, rs878854466, rs886038978, rs746972765, rs886039303, rs886040965, rs886040966, rs886040967, rs886229659, rs1553781304, rs1060502531, rs1553795301, rs1553803235, rs-1, rs1213452826, rs869025352, rs1553780501, rs1553785222, rs1382893400, rs1554841990, rs1430822242, rs1567692384, rs1576422965, rs1596712899, rs2059732940, rs2041090817, rs1439991530	27899403, 20622881

Unknown
Disease name	Disease term	dbSNP ID	References
Lung neoplasms	Lung Neoplasms		22046421
Prostatic neoplasms	Prostatic Neoplasms		18073375
Pulmonary thromboembolism	Pulmonary Thromboembolisms		20622881
Vascular diseases	Peripheral Vascular Diseases		20622881