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Aliases for DAB2 Gene

Aliases for DAB2 Gene

  • Dab, Mitogen-Responsive Phosphoprotein, Homolog 2 (Drosophila) 2 3
  • Doc2 3 4 6
  • Differentially Expressed In Ovarian Carcinoma 2 3 4
  • Differentially-Expressed Protein 2 3 4
  • Adaptor Molecule Disabled-2 3 4
  • DOC-2 3 4
  • Disabled (Drosophila) Homolog 2 (Mitogen-Responsive Phosphoprotein) 2
  • Disabled Homolog 2, Mitogen-Responsive Phosphoprotein (Drosophila) 2
  • Disabled Homolog 2, Mitogen-Responsive Phosphoprotein 3
  • Disabled Homolog 2 3

External Ids for DAB2 Gene

Summaries for DAB2 Gene

Entrez Gene Summary for DAB2 Gene

  • This gene encodes a mitogen-responsive phosphoprotein. It is expressed in normal ovarian epithelial cells, but is down-regulated or absent from ovarian carcinoma cell lines, suggesting its role as a tumor suppressor. This protein binds to the SH3 domains of GRB2, an adaptor protein that couples tyrosine kinase receptors to SOS (a guanine nucleotide exchange factor for Ras), via its C-terminal proline-rich sequences, and may thus modulate growth factor/Ras pathways by competing with SOS for binding to GRB2. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

GeneCards Summary for DAB2 Gene

DAB2 (Dab, Mitogen-Responsive Phosphoprotein, Homolog 2 (Drosophila)) is a Protein Coding gene. Among its related pathways are Tyrosine Kinases / Adaptors and Endocytosis. GO annotations related to this gene include protein C-terminus binding and SMAD binding. An important paralog of this gene is DAB1.

UniProtKB/Swiss-Prot for DAB2 Gene

  • Adapter protein that functions as clathrin-associated sorting protein (CLASP) required for clathrin-mediated endocytosis of selected cargo proteins. Can bind and assemble clathrin, and binds simultaneously to phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and cargos containg non-phosphorylated NPXY internalization motifs, such as the LDL receptor, to recruit them to clathrin-coated pits. Can function in clathrin-mediated endocytosis independently of the AP-2 complex. Involved in endocytosis of integrin beta-1; this function seems to redundant with the AP-2 complex and seems to require DAB2 binding to endocytosis accessory EH domain-containing proteins such as EPS15, EPS15L1 and ITSN1. Involved in endocytosis of cystic fibrosis transmembrane conductance regulator/CFTR. Involved in endocytosis of megalin/LRP2 lipoprotein receptor during embryonal development. Required for recycling of the TGF-beta receptor. Involved in CFTR trafficking to the late endosome. Involved in several receptor-mediated signaling pathways. Involved in TGF-beta receptor signaling and facilitates phosphorylation of the signal transducer SMAD2. Mediates TFG-beta-stimulated JNK activation. May inhibit the canoniocal Wnt/beta-catenin signaling pathway by stabilizing the beta-catenin destruction complex through a competing association with axin preventing its dephosphorylation through protein phosphatase 1 (PP1). Sequesters LRP6 towards clathrin-mediated endocytosis, leading to inhibition of Wnt/beta-catenin signaling. May activate non-canonical Wnt signaling. In cell surface growth factor/Ras signaling pathways proposed to inhibit ERK activation by interrupting the binding of GRB2 to SOS1 and to inhibit SRC by preventing its activating phosphorylation at Tyr-419. Proposed to be involved in modulation of androgen receptor (AR) signaling mediated by SRC activation; seems to compete with AR for interaction with SRC. Plays a role in the CSF-1 signal transduction pathway. Plays a role in cellular differentiation. Involved in cell positioning and formation of visceral endoderm (VE) during embryogenesis and proposed to be required in the VE to respond to Nodal signaling coming from the epiblast. Required for the epithelial to mesenchymal transition, a process necessary for proper embryonic development. May be involved in myeloid cell differentiation and can induce macrophage adhesion and spreading. May act as a tumor suppressor.

Gene Wiki entry for DAB2 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for DAB2 Gene

Genomics for DAB2 Gene

Genomic Location for DAB2 Gene

Start:
39,371,674 bp from pter
End:
39,462,300 bp from pter
Size:
90,627 bases
Orientation:
Minus strand

Genomic View for DAB2 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for DAB2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for DAB2 Gene

Regulatory Elements for DAB2 Gene

Proteins for DAB2 Gene

  • Protein details for DAB2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P98082-DAB2_HUMAN
    Recommended name:
    Disabled homolog 2
    Protein Accession:
    P98082
    Secondary Accessions:
    • A6NES5
    • Q13598
    • Q9BTY0
    • Q9UK04

    Protein attributes for DAB2 Gene

    Size:
    770 amino acids
    Molecular mass:
    82448 Da
    Quaternary structure:
    • Interacts (via NPXY motif) with DAB2 (via PID domain). Can interact (via PID domain) with LDLR, APP, APLP1 and APLP2, and weakly with INPP5D (via NPXY motifs); the interaction is impaired by tyrosine phosphorylation of the respective NPXY motifs. Can weakly interact (via PID domain) with LRP1 (via NPXY motif); the interaction is enhanced by tyrosine phosphorylation of the NPXY motif. Interacts with LRP2 (via NPXY motif); the interaction is not affected by tyrosine phosphorylation of the NPXY motif. Interacts with clathrin; in vitro can assemble clathrin triskelia into polyhedral coats. Interacts with AP2A2, ITGB1, ITGB3, ITGB5, PIAS2, DAB2IP, NOSTRIN, FCHO1, DVL3, EPS15, ITSN1 and EPS15L1. Interacts with SH3KBP1 (via SH3 domains). Interacts with GRB2; competes with SOS1 for binding to GRB2 and the interaction is enhanced by EGF and NT-3 stimulation. Interacts with MAP3K7; the interaction is induced by TGF-beta stimulation and may mediate TGF-beta stimulated JNK activation. Interacts with AXIN1 and PPP1CA; the interactions are mutually exclusive. Interacts with the globular tail of MYO6. Interacts (via DPF motifs) with FCHO2; the interaction is direct and required for DAB2-mediated LDLR endocytosis. Interacts with LRP6; the interaction involves LRP6 phosphorylation by CK2 and sequesters LRP6 towards clathrin-mediated endocytosis. Associates with the TGF-beta receptor complex (Probable). Interacts with SMAD2 and SMAD3; the interactions are enhanced upon TGF-beta stimulation. Interacts with GRB2; the interaction is enhanced by EGF and NT-3 stimulation. Interacts with SRC; the interaction is enhanced by EGF stimulation.

    Three dimensional structures from OCA and Proteopedia for DAB2 Gene

    Alternative splice isoforms for DAB2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for DAB2 Gene

Proteomics data for DAB2 Gene at MOPED

Post-translational modifications for DAB2 Gene

  • Phosphorylated. Phosphorylation during mitosis is leading to membrane displacement (By similarity).
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for DAB2 Gene

No data available for DME Specific Peptides for DAB2 Gene

Domains for DAB2 Gene

Protein Domains for DAB2 Gene

UniProtKB/Swiss-Prot:

DAB2_HUMAN
Domain:
  • The PID domain binds to predominantly non-phosphorylated NPXY internalization motifs present in members of the LDLR and APP family; it also mediates simultaneous binding to phosphatidylinositol 4,5-bisphosphate.:
    • P98082
  • The Asn-Pro-Phe (NPF) motifs, which are found in proteins involved in the endocytic pathway, mediate the interaction with the EH domain of EPS15, EPS15R and ITSN1.:
    • P98082
  • Contains 1 PID domain.:
    • P98082
genes like me logo Genes that share domains with DAB2: view

No data available for Gene Families for DAB2 Gene

Function for DAB2 Gene

Molecular function for DAB2 Gene

GENATLAS Biochemistry: murine disabled-2,mitogen responsive-phosphoprotein p96 homolog,originally identified as a cDNA fragment isolated from normal ovarian epithelial cell,expressed in various tissues,putatively involved in cellular transduction
UniProtKB/Swiss-Prot Function: Adapter protein that functions as clathrin-associated sorting protein (CLASP) required for clathrin-mediated endocytosis of selected cargo proteins. Can bind and assemble clathrin, and binds simultaneously to phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and cargos containg non-phosphorylated NPXY internalization motifs, such as the LDL receptor, to recruit them to clathrin-coated pits. Can function in clathrin-mediated endocytosis independently of the AP-2 complex. Involved in endocytosis of integrin beta-1; this function seems to redundant with the AP-2 complex and seems to require DAB2 binding to endocytosis accessory EH domain-containing proteins such as EPS15, EPS15L1 and ITSN1. Involved in endocytosis of cystic fibrosis transmembrane conductance regulator/CFTR. Involved in endocytosis of megalin/LRP2 lipoprotein receptor during embryonal development. Required for recycling of the TGF-beta receptor. Involved in CFTR trafficking to the late endosome. Involved in several receptor-mediated signaling pathways. Involved in TGF-beta receptor signaling and facilitates phosphorylation of the signal transducer SMAD2. Mediates TFG-beta-stimulated JNK activation. May inhibit the canoniocal Wnt/beta-catenin signaling pathway by stabilizing the beta-catenin destruction complex through a competing association with axin preventing its dephosphorylation through protein phosphatase 1 (PP1). Sequesters LRP6 towards clathrin-mediated endocytosis, leading to inhibition of Wnt/beta-catenin signaling. May activate non-canonical Wnt signaling. In cell surface growth factor/Ras signaling pathways proposed to inhibit ERK activation by interrupting the binding of GRB2 to SOS1 and to inhibit SRC by preventing its activating phosphorylation at Tyr-419. Proposed to be involved in modulation of androgen receptor (AR) signaling mediated by SRC activation; seems to compete with AR for interaction with SRC. Plays a role in the CSF-1 signal transduction pathway. Plays a role in cellular differentiation. Involved in cell positioning and formation of visceral endoderm (VE) during embryogenesis and proposed to be required in the VE to respond to Nodal signaling coming from the epiblast. Required for the epithelial to mesenchymal transition, a process necessary for proper embryonic development. May be involved in myeloid cell differentiation and can induce macrophage adhesion and spreading. May act as a tumor suppressor.

Gene Ontology (GO) - Molecular Function for DAB2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005178 integrin binding IEA --
GO:0005515 protein binding IPI 11387212
GO:0005546 phosphatidylinositol-4,5-bisphosphate binding IEA --
GO:0008022 protein C-terminus binding IPI 15837803
GO:0030276 clathrin binding --
genes like me logo Genes that share ontologies with DAB2: view
genes like me logo Genes that share phenotypes with DAB2: view

Animal Models for DAB2 Gene

MGI Knock Outs for DAB2:

miRNA for DAB2 Gene

miRTarBase miRNAs that target DAB2

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targeting and HOMER Transcription for DAB2 Gene

Localization for DAB2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for DAB2 Gene

Cytoplasm. Cytoplasmic vesicle, clathrin-coated vesicle membrane. Membrane, clathrin-coated pit. Note=Colocalizes with large insert-containing isoforms of MYO6 at clathrin-coated pits/vesicles. During mitosis is progressively displaced from the membrane and translocated to the cytoplasm.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for DAB2 Gene COMPARTMENTS Subcellular localization image for DAB2 gene
Compartment Confidence
lysosome 4
plasma membrane 4
vacuole 4
cytosol 3
nucleus 3
cytoskeleton 1
endosome 1
extracellular 1

Gene Ontology (GO) - Cellular Components for DAB2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus --
GO:0005730 nucleolus IDA --
GO:0005737 cytoplasm --
GO:0005765 lysosomal membrane TAS --
GO:0005886 plasma membrane TAS --
genes like me logo Genes that share ontologies with DAB2: view

Pathways for DAB2 Gene

genes like me logo Genes that share pathways with DAB2: view

Gene Ontology (GO) - Biological Process for DAB2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000904 cell morphogenesis involved in differentiation IEA --
GO:0001701 in utero embryonic development IEA --
GO:0001921 positive regulation of receptor recycling IEA --
GO:0001934 positive regulation of protein phosphorylation IMP 12805222
GO:0006898 receptor-mediated endocytosis IEA --
genes like me logo Genes that share ontologies with DAB2: view

Compounds for DAB2 Gene

(4) Novoseek inferred chemical compound relationships for DAB2 Gene

Compound -log(P) Hits PubMed IDs
phosphotyrosine 47.7 4
retinoic acid 37.4 4
fibrinogen 14.7 7
zinc 0 1
genes like me logo Genes that share compounds with DAB2: view

Transcripts for DAB2 Gene

mRNA/cDNA for DAB2 Gene

Unigene Clusters for DAB2 Gene

Dab, mitogen-responsive phosphoprotein, homolog 2 (Drosophila):
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for DAB2 Gene

ExUns: 1a · 1b · 1c ^ 2 ^ 3a · 3b ^ 4 ^ 5 ^ 6a · 6b · 6c ^ 7a · 7b ^ 8a · 8b ^ 9a · 9b ^ 10 ^ 11a · 11b ^ 12a · 12b ^ 13 ^ 14 ^ 15a · 15b ^
SP1: - - - - - - -
SP2: -
SP3:
SP4: - - - - -
SP5: - - - - - -
SP6: - - -
SP7:
SP8: - - - -
SP9: -
SP10:
SP11:
SP12: -
SP13:
SP14:
SP15: - - -

ExUns: 16 ^ 17 ^ 18 ^ 19a · 19b ^ 20
SP1:
SP2:
SP3:
SP4:
SP5:
SP6:
SP7:
SP8:
SP9:
SP10:
SP11:
SP12:
SP13:
SP14: -
SP15:

Relevant External Links for DAB2 Gene

GeneLoc Exon Structure for
DAB2
ECgene alternative splicing isoforms for
DAB2

Expression for DAB2 Gene

mRNA expression in normal human tissues for DAB2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for DAB2 Gene

This gene is overexpressed in Kidney - Cortex (4.4) and Adrenal Gland (4.2).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for DAB2 Gene

SOURCE GeneReport for Unigene cluster for DAB2 Gene Hs.696631

mRNA Expression by UniProt/SwissProt for DAB2 Gene

P98082-DAB2_HUMAN
Tissue specificity: Expressed in deep invaginations, inclusion cysts and the surface epithelial cells of the ovary. Also expressed in breast epithelial cells, spleen, thymus, prostate, testis, macrophages, fibroblasts, lung epithelial cells, placenta, brain stem, heart and small intestine. Expressed in kidney proximal tubular epithelial cells (at protein level).
genes like me logo Genes that share expressions with DAB2: view

Orthologs for DAB2 Gene

This gene was present in the common ancestor of animals.

Orthologs for DAB2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia DAB2 36
  • 99.35 (n)
  • 99.22 (a)
DAB2 37
  • 99 (a)
OneToOne
cow
(Bos Taurus)
Mammalia DAB2 36
  • 89.54 (n)
  • 86.59 (a)
DAB2 37
  • 87 (a)
OneToOne
dog
(Canis familiaris)
Mammalia DAB2 36
  • 91.6 (n)
  • 89.87 (a)
DAB2 37
  • 83 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Dab2 36
  • 85.58 (n)
  • 84.01 (a)
Dab2 16
Dab2 37
  • 84 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia DAB2 37
  • 66 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia DAB2 37
  • 73 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Dab2 36
  • 86.41 (n)
  • 84.01 (a)
chicken
(Gallus gallus)
Aves DAB2 36
  • 70.87 (n)
  • 67.34 (a)
DAB2 37
  • 63 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia DAB2 37
  • 58 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia dab2 36
  • 66.97 (n)
  • 63.34 (a)
zebrafish
(Danio rerio)
Actinopterygii dab2 37
  • 44 (a)
OneToOne
Dr.9443 36
si:ch211-204c21.1 36
  • 58.77 (n)
  • 54.28 (a)
fruit fly
(Drosophila melanogaster)
Insecta Dab 37
  • 4 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea dab-1 37
  • 4 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 37
  • 6 (a)
OneToMany
Species with no ortholog for DAB2:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for DAB2 Gene

ENSEMBL:
Gene Tree for DAB2 (if available)
TreeFam:
Gene Tree for DAB2 (if available)

Paralogs for DAB2 Gene

Paralogs for DAB2 Gene

genes like me logo Genes that share paralogs with DAB2: view

Variants for DAB2 Gene

Sequence variations from dbSNP and Humsavar for DAB2 Gene

SNP ID Clin Chr 05 pos Sequence Context AA Info Type MAF
rs4578 -- 39,373,151(-) ACCCT(A/G)CCTCT utr-variant-3-prime
rs9487 -- 39,373,399(-) CAGAG(A/G)AATAA utr-variant-3-prime
rs14454 -- 39,371,766(+) CAAAA(A/C)AGTTG utr-variant-3-prime
rs700239 -- 39,373,587(+) AAATG(A/C)TTAGC intron-variant
rs700240 -- 39,374,813(+) TTTTT(G/T)GATGT intron-variant

Structural Variations from Database of Genomic Variants (DGV) for DAB2 Gene

Variant ID Type Subtype PubMed ID
nsv327295 CNV Insertion 16902084
esv1006481 CNV Insertion 20482838
esv1469374 CNV Insertion 17803354
nsv327367 CNV Insertion 16902084

Relevant External Links for DAB2 Gene

HapMap Linkage Disequilibrium report
DAB2
Human Gene Mutation Database (HGMD)
DAB2

Disorders for DAB2 Gene

(11) Novoseek inferred disease relationships for DAB2 Gene

Disease -log(P) Hits PubMed IDs
ovarian carcinoma 56.5 8
teratocarcinoma 56.2 1
ovarian cancer 35.6 5
epithelial tumor 29.5 2
premalignant 22.4 4

Relevant External Links for DAB2

Genetic Association Database (GAD)
DAB2
Human Genome Epidemiology (HuGE) Navigator
DAB2
genes like me logo Genes that share disorders with DAB2: view

No data available for UniProtKB/Swiss-Prot for DAB2 Gene

Publications for DAB2 Gene

  1. DOC-2, a candidate tumor suppressor gene in human epithelial ovarian cancer. (PMID: 9620555) Mok S.C. … Berkowitz R.S. (Oncogene 1998) 2 3 4 23
  2. Sequence, genomic structure, and chromosomal assignment of human DOC- 2. (PMID: 8660969) Albertsen H.M. … White R. (Genomics 1996) 2 3 4 23
  3. Disabled-2 inactivation is an early step in ovarian tumorigenicity. (PMID: 10340382) Fazili Z. … Xu X.-X. (Oncogene 1999) 3 4 23
  4. Cytosolic adaptor protein Dab2 is an intracellular ligand of endocytic receptor gp600/megalin. (PMID: 10769163) Oleinikov A.V. … Makker S.P. (Biochem. J. 2000) 3 4 23
  5. The adaptor molecule Disabled-2 links the transforming growth factor beta receptors to the Smad pathway. (PMID: 11387212) Hocevar B.A. … Howe P.H. (EMBO J. 2001) 3 4 23

Products for DAB2 Gene

Sources for DAB2 Gene

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