| Tbio | Disabled homolog 1 |
Adapter molecule functioning in neural development. May regulate SIAH1 activity (By similarity).
The laminar organization of multiple neuronal types in the cerebral cortex is required for normal cognitive function. In mice, the disabled-1 gene plays a central role in brain development, directing the migration of cortical neurons past previously formed neurons to reach their proper layer. This gene is similar to disabled-1, and the protein encoded by this gene is thought to be a signal transducer that interacts with protein kinase pathways to regulate neuronal positioning in the developing brain. Alternatively spliced transcript variants of this gene have been reported, but their full length nature has not been determined. [provided by RefSeq, Jul 2008]
The laminar organization of multiple neuronal types in the cerebral cortex is required for normal cognitive function. In mice, the disabled-1 gene plays a central role in brain development, directing the migration of cortical neurons past previously formed neurons to reach their proper layer. This gene is similar to disabled-1, and the protein encoded by this gene is thought to be a signal transducer that interacts with protein kinase pathways to regulate neuronal positioning in the developing brain. Alternatively spliced transcript variants of this gene have been reported, but their full length nature has not been determined. [provided by RefSeq, Jul 2008]
Comments
| Disease | Target Count |
|---|---|
| Autistic Disorder | 320 |
| Disease | Target Count | P-value |
|---|---|---|
| posterior fossa group A ependymoma | 1511 | 1.5e-14 |
| osteosarcoma | 7933 | 3.6e-07 |
| interstitial cystitis | 2299 | 1.4e-05 |
| atypical teratoid / rhabdoid tumor | 4369 | 4.7e-04 |
| group 3 medulloblastoma | 2254 | 7.6e-04 |
| oligodendroglioma | 2849 | 1.1e-03 |
| astrocytic glioma | 2241 | 1.1e-03 |
| adult high grade glioma | 2148 | 1.1e-03 |
| glioblastoma | 5572 | 2.1e-03 |
| intraductal papillary-mucinous adenoma (IPMA) | 2956 | 2.7e-03 |
| medulloblastoma, large-cell | 6234 | 6.4e-03 |
| subependymal giant cell astrocytoma | 2287 | 2.4e-02 |
| Breast cancer | 3098 | 3.1e-02 |
| lung cancer | 4473 | 4.4e-02 |
| Disease | Target Count | Z-score | Confidence |
|---|---|---|---|
| Anorexia nervosa | 59 | 0.0 | 1.0 |
| Kawasaki disease | 24 | 0.0 | 1.0 |
| Motor neuron disease | 39 | 0.0 | 1.0 |
| Disease | log2 FC | p |
|---|---|---|
| astrocytic glioma | -2.200 | 1.1e-03 |
| posterior fossa group A ependymoma | -3.400 | 1.5e-14 |
| oligodendroglioma | -2.000 | 1.1e-03 |
| glioblastoma | -2.400 | 2.1e-03 |
| osteosarcoma | 1.176 | 3.6e-07 |
| atypical teratoid / rhabdoid tumor | -2.200 | 4.7e-04 |
| medulloblastoma, large-cell | 1.200 | 6.4e-03 |
| intraductal papillary-mucinous adenoma (... | -1.100 | 2.7e-03 |
| lung cancer | -1.100 | 4.4e-02 |
| interstitial cystitis | -2.500 | 1.4e-05 |
| adult high grade glioma | -2.300 | 1.1e-03 |
| group 3 medulloblastoma | 2.600 | 7.6e-04 |
| subependymal giant cell astrocytoma | -2.665 | 2.4e-02 |
| Breast cancer | -2.100 | 3.1e-02 |
| PMID | Text | |
|---|---|---|
| 26270645 | Study shows that early neural cells transiently express Reelin at the time they leave the presumptive olfactory/vomeronasal epithelium and that Dab 1 is present in the migratory cell mass and in the presumptive ensheathing cells in the absence of reelin. | |
| 26028559 | this study is the first to provide genetic evidence for DAB1 as a candidate AD liability/protection gene, although the strength of the contribution of DAB1 may differ among populations | |
| 24844606 | results of this study demonstrated the presence of reelin, its receptors VLDLR and ApoER2 as well as Dab1 in the ENS and might indicate a novel role of the reelin system in regulating neuronal plasticity and pre-synaptic functions in the ENS. | |
| 23333377 | The finding of this study suggested that variations in DAB1 involved in the Reelin signaling pathway might contribute to genetic susceptibility to autism with Chinese Han decent. | |
| 22419519 | Variation in genes encoding proteins at the gateway of Reelin signaling: ligands RELN and APOE, their common receptors APOER2 and VLDLR, and adaptor DAB1, was examined. | |
| 22394407 | show that Reelin-stimulated Notch-1 activation is dependent on Reelin signaling | |
| 22163036 | alternative splicing of Dab1 is conserved in avian and mammalian species, with Dab1-L driving SFK phosphorylation in both species | |
| 21453247 | we report for the first time, that DAB1 is significantly up-regulated in human frontal cortex brain samples of Alzheimer disease patients | |
| 21315259 | Dab1, an essential component of the reelin pathway, is required for glia-independent somal translocation in the neocortex. | |
| 20628086 | Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator) | |
| 20600896 | Observational study and genome-wide association study of gene-disease association. (HuGE Navigator) | |
| 20568118 | Fe65 and Dab1 compete for binding to APP. Dab1 significantly decreased the amount of APP bound to LRP and the level of secreted APP and APP-CTF in LRP expressing cells | |
| 20379614 | Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator) | |
| 19913121 | Observational study of gene-disease association. (HuGE Navigator) | |
| 19853035 | Thus, the present observations suggest a correlation between Dab1 phosphorylation, Abeta deposition and PrP(sc) type in sCJD. | |
| 19116273 | ligation of ApoER2 by APC signals via Dab1 phosphorylation and subsequent activation of PI3K and Akt and inactivation of GSK3beta, thereby contributing to APC's beneficial effects on cells. | |
| 18519826 | Clinical trial and genome-wide association study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator) | |
| 18089558 | Fyn, due in part to its effects on Dab1, regulates the phosphorylation, trafficking, and processing of APP and apoEr2. | |
| 18008369 | Resides within an unstable common fragile site region and might play a role in human tumorigenesis. | |
| 17974915 | Cul5 plays an essential role in regulating neuron migrations during cortical development, possibly by opposing a promigratory effect of Dab1. | |
| 17548821 | DAB1 phosphorylation occurs solely in the segment spanning the 5th and 6th reelin repeats. | |
| 17062576 | results suggest that the mouse ortholog is a nucleocytoplasmic shuttling protein | |
| 16951405 | The effect of Dab1 on APP and apoEr2 processing in transfected cells and primary neurons is reported. | |
| 16481437 | After Reelin binds to the receptors, Disabled-1 becomes phosphorylated on tyrosine residues, initiating a signaling cascade that includes activation of Src-family kinases and Akt. | |
| 15883038 | phosphoinositide-binding region within Dab1 PTB domain is required for membrane localization and basal tyrosine phosphorylation of Dab1 | |
| 15718228 | Dab1 regulates both cell surface expression and internalization of Reelin receptors | |
| 15175076 | significantly lower levels of disabled homolog 1 gene transcripts were detected in gangliogliomas compared to controls | |
| 14961563 | Dab1 immunoreactivity is found in certain populations of amacrine cells of the retina, with lobular appendages in the outer half of the inner plexiform layer (IPL) and a bushy, smooth dendritic tree in the inner half of the IPL. | |
| 12834112 | RELN and DAB1 coexpression in these neurons is necessary for both normal cortical development and mature function. | |
| 12581169 | involvement of disabled homolog 1 in neurogenesis | |
| 12446734 | This gene, is an intracellular adaptor of the Reelin pathway and reveals unusual complexity in human and mouse. |
MSTETELQVAVKTSAKKDSRKKGQDRSEATLIKRFKGEGVRYKAKLIGIDEVSAARGDKLCQDSMMKLKG 1 - 70 VVAGARSKGEHKQKIFLTISFGGIKIFDEKTGALQHHHAVHEISYIAKDITDHRAFGYVCGKEGNHRFVA 71 - 140 IKTAQAAEPVILDLRDLFQLIYELKQREELEKKAQKDKQCEQAVYQTILEEDVEDPVYQYIVFEAGHEPI 141 - 210 RDPETEENIYQVPTSQKKEGVYDVPKSQPVSNGYSFEDFEERFAAATPNRNLPTDFDEIFEATKAVTQLE 211 - 280 LFGDMSTPPDITSPPTPATPGDAFIPSSSQTLPASADVFSSVPFGTAAVPSGYVAMGAVLPSFWGQQPLV 281 - 350 QQQMVMGAQPPVAQVMPGAQPIAWGQPGLFPATQQPWPTVAGQFPPAAFMPTQTVMPLPAAMFQGPLTPL 351 - 420 ATVPGTSDSTRSSPQTDKPRQKMGKETFKDFQMAQPPPVPSRKPDQPSLTCTSEAFSSYFNKVGVAQDTD 421 - 490 DCDDFDISQLNLTPVTSTTPSTNSPPTPAPRQSSPSKSSASHASDPTTDDIFEEGFESPSKSEEQEAPDG 491 - 560 SQASSNSDPFGEPSGEPSGDNISPQAGS 561 - 588 //
| PMID | Year | Title | |
|---|---|---|---|
| 26441085 | 2015 | AKT-independent Reelin signaling requires interactions of heterotrimeric Go and Src. | |
| 26270645 | 2015 | Human Neural Cells Transiently Express Reelin during Olfactory Placode Development. | |
| 26028559 | 2015 | Functional enrichment analysis of three Alzheimer's disease genome-wide association studies identities DAB1 as a novel candidate liability/protective gene. | |
| 25416956 | 2014 | A proteome-scale map of the human interactome network. | |
| 24962325 | 2014 | Genome-wide survival analysis of age at onset of alcohol dependence in extended high-risk COGA families. | |
| 24844606 | 2014 | Expression and regulation of reelin and its receptors in the enteric nervous system. | |
| 24535457 | 2014 | A genome-wide association meta-analysis of plasma A? peptides concentrations in the elderly. | |
| 24324551 | 2013 | Genome wide association study (GWAS) of Chagas cardiomyopathy in Trypanosoma cruzi seropositive subjects. | |
| 23568457 | 2013 | Genetic variants associated with disordered eating. | |
| 23449627 | 2013 | Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity. | |
| 23333377 | 2013 | Association study between genes in Reelin signaling pathway and autism identifies DAB1 as a susceptibility gene in a Chinese Han population. | |
| 22610502 | 2012 | Genome-wide analysis of polymorphisms associated with cytokine responses in smallpox vaccine recipients. | |
| 22419519 | 2012 | Impact of the Reelin signaling cascade (ligands-receptors-adaptor complex) on cognition in schizophrenia. | |
| 22394407 | 2012 | Reelin regulates differentiation of neural stem cells by activation of notch signaling through Disabled-1 tyrosine phosphorylation. | |
| 22163036 | 2011 | Disabled-1 alternative splicing in human fetal retina and neural tumors. | |
| 21453247 | 2011 | The AICD interacting protein DAB1 is up-regulated in Alzheimer frontal cortex brain samples and causes deregulation of proteins involved in gene expression changes. | |
| 21315259 | 2011 | Reelin regulates cadherin function via Dab1/Rap1 to control neuronal migration and lamination in the neocortex. | |
| 21221998 | 2011 | A genome-wide association analysis reveals 1p31 and 2p13.3 as susceptibility loci for Kawasaki disease. | |
| 20628086 | 2010 | Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. | |
| 20600896 | 2010 | Genome-wide association study of vitamin D concentrations in Hispanic Americans: the IRAS family study. | |
| 20568118 | 2010 | Dab1 binds to Fe65 and diminishes the effect of Fe65 or LRP1 on APP processing. | |
| 20379614 | Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. | ||
| 20041166 | 2009 | Common genetic variation and the control of HIV-1 in humans. | |
| 19913121 | 2009 | Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip. | |
| 19853035 | 2010 | Involvement of Dab1 in APP processing and beta-amyloid deposition in sporadic Creutzfeldt-Jakob patients. | |
| 19116273 | 2009 | Activated protein C ligation of ApoER2 (LRP8) causes Dab1-dependent signaling in U937 cells. | |
| 18519826 | 2008 | Molecular genetics of successful smoking cessation: convergent genome-wide association study results. | |
| 18089558 | 2008 | Fyn modulation of Dab1 effects on amyloid precursor protein and ApoE receptor 2 processing. | |
| 18008369 | 2008 | Disabled-1 is a large common fragile site gene, inactivated in multiple cancers. | |
| 17974915 | 2007 | Cullin 5 regulates Dab1 protein levels and neuron positioning during cortical development. | |
| 17548821 | 2007 | Structure of a receptor-binding fragment of reelin and mutational analysis reveal a recognition mechanism similar to endocytic receptors. | |
| 17062576 | 2006 | Mouse Disabled1 (DAB1) is a nucleocytoplasmic shuttling protein. | |
| 16951405 | 2006 | DAB1 and Reelin effects on amyloid precursor protein and ApoE receptor 2 trafficking and processing. | |
| 16710414 | 2006 | The DNA sequence and biological annotation of human chromosome 1. | |
| 16481437 | 2006 | Functional dissection of Reelin signaling by site-directed disruption of Disabled-1 adaptor binding to apolipoprotein E receptor 2: distinct roles in development and synaptic plasticity. | |
| 15883038 | 2005 | Signaling through Disabled 1 requires phosphoinositide binding. | |
| 15718228 | 2005 | Disabled1 regulates the intracellular trafficking of reelin receptors. | |
| 15489334 | 2004 | The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). | |
| 15272003 | 2004 | Serine and threonine phosphorylation of the low density lipoprotein receptor-related protein by protein kinase Calpha regulates endocytosis and association with adaptor molecules. | |
| 15175076 | 2004 | The reelin pathway components disabled-1 and p35 in gangliogliomas--a mutation and expression analysis. | |
| 15062102 | 2004 | Activation of a Dab1/CrkL/C3G/Rap1 pathway in Reelin-stimulated neurons. | |
| 14961563 | 2004 | AII amacrine cells in the mammalian retina show disabled-1 immunoreactivity. | |
| 14702039 | 2004 | Complete sequencing and characterization of 21,243 full-length human cDNAs. | |
| 14578885 | 2003 | Interaction of reelin signaling and Lis1 in brain development. | |
| 12834112 | 2003 | Reelin and disabled-1 expression in developing and mature human cortical neurons. | |
| 12646221 | 2003 | Inhibition of ubiquitin ligase Siah-1A by disabled-1. | |
| 12606711 | 2003 | Integrin beta cytoplasmic domain interactions with phosphotyrosine-binding domains: a structural prototype for diversity in integrin signaling. | |
| 12581169 | 2003 | Disabled-1 mRNA and protein expression in developing human cortex. | |
| 12477932 | 2002 | Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. | |
| 12446734 | 2003 | The gene encoding disabled-1 (DAB1), the intracellular adaptor of the Reelin pathway, reveals unusual complexity in human and mouse. | |
| 12077184 | 2002 | Cyclin-dependent kinase 5 phosphorylates disabled 1 independently of Reelin signaling. | |
| 11812785 | 2002 | The mechanism of growth-inhibitory effect of DOC-2/DAB2 in prostate cancer. Characterization of a novel GTPase-activating protein associated with N-terminal domain of DOC-2/DAB2. | |
| 11716507 | 2001 | Disabled-1 interacts with a novel developmentally regulated protocadherin. | |
| 11279201 | 2001 | Identification of reelin-induced sites of tyrosyl phosphorylation on disabled 1. | |
| 11137154 | 2000 | The evolution of cortical development. An hypothesis based on the role of the Reelin signaling pathway. | |
| 10959835 | 2000 | Dab1 tyrosine phosphorylation sites relay positional signals during mouse brain development. | |
| 10827173 | 2000 | Interactions of the low density lipoprotein receptor gene family with cytosolic adaptor and scaffold proteins suggest diverse biological functions in cellular communication and signal transduction. | |
| 10460257 | 1999 | Disabled-1 binds to the cytoplasmic domain of amyloid precursor-like protein 1. | |
| 10380922 | 1999 | Reeler/Disabled-like disruption of neuronal migration in knockout mice lacking the VLDL receptor and ApoE receptor 2. | |
| 10373567 | 1999 | The disabled 1 phosphotyrosine-binding domain binds to the internalization signals of transmembrane glycoproteins and to phospholipids. | |
| 9837937 | 1998 | Interaction of cytosolic adaptor proteins with neuronal apolipoprotein E receptors and the amyloid precursor protein. | |
| 9790777 | 1998 | Cloning of human DAB1 and mapping to chromosome 1p31-p32. | |
| 9716537 | 1998 | Disabled-1 acts downstream of Reelin in a signaling pathway that controls laminar organization in the mammalian brain. |
