Human Gene DAB2 (ENST00000320816.11) from GENCODE V44
  Description: Homo sapiens DAB adaptor protein 2 (DAB2), transcript variant 1, mRNA. (from RefSeq NM_001343)
RefSeq Summary (NM_001343): 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].
Gencode Transcript: ENST00000320816.11
Gencode Gene: ENSG00000153071.15
Transcript (Including UTRs)
   Position: hg38 chr5:39,371,677-39,424,980 Size: 53,304 Total Exon Count: 15 Strand: -
Coding Region
   Position: hg38 chr5:39,375,019-39,394,320 Size: 19,302 Coding Exon Count: 13 

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RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr5:39,371,677-39,424,980)mRNA (may differ from genome)Protein (770 aa)
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-  Comments and Description Text from UniProtKB
  ID: DAB2_HUMAN
DESCRIPTION: RecName: Full=Disabled homolog 2; AltName: Full=DOC-2; AltName: Full=Differentially-expressed protein 2;
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.
SUBUNIT: 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.
INTERACTION: P62993:GRB2; NbExp=2; IntAct=EBI-1171238, EBI-401755; P16333:NCK1; NbExp=2; IntAct=EBI-1171238, EBI-389883; Q15796:SMAD2; NbExp=4; IntAct=EBI-1171238, EBI-1040141; P84022:SMAD3; NbExp=3; IntAct=EBI-1171238, EBI-347161;
SUBCELLULAR LOCATION: 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.
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).
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 (By similarity).
DOMAIN: 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 (By similarity).
PTM: Phosphorylated. Phosphorylation during mitosis is leading to membrane displacement (By similarity).
SIMILARITY: Contains 1 PID domain.

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-  MalaCards Disease Associations
  MalaCards Gene Search: DAB2
Diseases sorted by gene-association score: malignant epithelial mesothelioma (11), deafness, autosomal dominant 22 (6), deafness, autosomal recessive 37 (6), ovarian cancer, somatic (4), cystic fibrosis (2)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 69.23 RPKM in Cells - Cultured fibroblasts
Total median expression: 675.00 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -109.50278-0.394 Picture PostScript Text
3' UTR -432.801754-0.247 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR011993 - PH_like_dom
IPR006020 - PTyr_interaction_dom

Pfam Domains:
PF00640 - Phosphotyrosine interaction domain (PTB/PID)

Protein Data Bank (PDB) 3-D Structure
MuPIT help
2LSW - NMR MuPIT


ModBase Predicted Comparative 3D Structure on P98082
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserGenome BrowserNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGDEnsembl   
Protein SequenceProtein SequenceProtein Sequence   
AlignmentAlignmentAlignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005515 protein binding
GO:0008022 protein C-terminus binding
GO:0035615 clathrin adaptor activity
GO:0038024 cargo receptor activity
GO:0046332 SMAD binding

Biological Process:
GO:0001934 positive regulation of protein phosphorylation
GO:0006897 endocytosis
GO:0006898 receptor-mediated endocytosis
GO:0006915 apoptotic process
GO:0007275 multicellular organism development
GO:0008283 cell proliferation
GO:0010718 positive regulation of epithelial to mesenchymal transition
GO:0010862 positive regulation of pathway-restricted SMAD protein phosphorylation
GO:0015031 protein transport
GO:0016055 Wnt signaling pathway
GO:0030154 cell differentiation
GO:0030335 positive regulation of cell migration
GO:0030511 positive regulation of transforming growth factor beta receptor signaling pathway
GO:0032091 negative regulation of protein binding
GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process
GO:0035026 leading edge cell differentiation
GO:0043066 negative regulation of apoptotic process
GO:0045807 positive regulation of endocytosis
GO:0045892 negative regulation of transcription, DNA-templated
GO:0045893 positive regulation of transcription, DNA-templated
GO:0060391 positive regulation of SMAD protein import into nucleus
GO:0060766 negative regulation of androgen receptor signaling pathway
GO:0061024 membrane organization
GO:0090090 negative regulation of canonical Wnt signaling pathway
GO:1903077 negative regulation of protein localization to plasma membrane
GO:2000096 positive regulation of Wnt signaling pathway, planar cell polarity pathway
GO:2000370 positive regulation of clathrin-dependent endocytosis
GO:2000643 positive regulation of early endosome to late endosome transport
GO:0007229 integrin-mediated signaling pathway

Cellular Component:
GO:0001650 fibrillar center
GO:0005737 cytoplasm
GO:0005765 lysosomal membrane
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0005905 clathrin-coated pit
GO:0005925 focal adhesion
GO:0016020 membrane
GO:0030136 clathrin-coated vesicle
GO:0030665 clathrin-coated vesicle membrane
GO:0031410 cytoplasmic vesicle
GO:0043231 intracellular membrane-bounded organelle
GO:0070022 transforming growth factor beta receptor complex


-  Descriptions from all associated GenBank mRNAs
  AK092836 - Homo sapiens cDNA FLJ35517 fis, clone SPLEN2000698.
AK130136 - Homo sapiens cDNA FLJ26626 fis, clone MPC03831.
JD033502 - Sequence 14526 from Patent EP1572962.
JD026396 - Sequence 7420 from Patent EP1572962.
U39050 - Human mitogen-responsive phosphoprotein (DOC-2) mRNA, complete cds.
U53446 - Human mitogen-responsive phosphoprotein DOC-2 mRNA, complete cds.
JD403706 - Sequence 384730 from Patent EP1572962.
AK123803 - Homo sapiens cDNA FLJ41809 fis, clone NOVAR2001844.
JD092973 - Sequence 73997 from Patent EP1572962.
JD284138 - Sequence 265162 from Patent EP1572962.
AF188298 - Homo sapiens disabled 2 p93 (DAB2) mRNA, alternatively spliced, complete cds.
JD239865 - Sequence 220889 from Patent EP1572962.
BC003064 - Homo sapiens disabled homolog 2, mitogen-responsive phosphoprotein (Drosophila), mRNA (cDNA clone MGC:1764 IMAGE:3504380), complete cds.
JD527745 - Sequence 508769 from Patent EP1572962.
AK297984 - Homo sapiens cDNA FLJ53147 complete cds, highly similar to Disabled homolog 2.
JD302427 - Sequence 283451 from Patent EP1572962.
KJ891023 - Synthetic construct Homo sapiens clone ccsbBroadEn_00417 DAB2 gene, encodes complete protein.
AK314381 - Homo sapiens cDNA, FLJ95154, highly similar to Homo sapiens disabled homolog 2, mitogen-responsive phosphoprotein (Drosophila) (DAB2), mRNA.
DQ891872 - Synthetic construct clone IMAGE:100004502; FLH180775.01X; RZPDo839F11134D disabled homolog 2, mitogen-responsive phosphoprotein (Drosophila) (DAB2) gene, encodes complete protein.
EU176643 - Synthetic construct Homo sapiens clone IMAGE:100011442; FLH180774.01L; RZPDo839A10254D disabled homolog 2, mitogen-responsive phosphoprotein (Drosophila) (DAB2) gene, encodes complete protein.
AB590149 - Synthetic construct DNA, clone: pFN21AB5784, Homo sapiens DAB2 gene for disabled homolog 2, mitogen-responsive phosphoprotein, without stop codon, in Flexi system.
L16886 - Human differentially expressed protein mRNA, partial cds.
CU678354 - Synthetic construct Homo sapiens gateway clone IMAGE:100020070 5' read DAB2 mRNA.
AK024965 - Homo sapiens cDNA: FLJ21312 fis, clone COL02175.
JD447412 - Sequence 428436 from Patent EP1572962.
JD282973 - Sequence 263997 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04144 - Endocytosis

Reactome (by CSHL, EBI, and GO)

Protein P98082 (Reactome details) participates in the following event(s):

R-HSA-196026 Dab2 is recruited to the junctional plaques
R-HSA-8863472 DAB2 binds LRP2
R-HSA-196017 Dynamin is recruited to the gap junction plaque
R-HSA-8863471 LDLR is bound by DAB2 and ARH
R-HSA-190519 Internalization of gap junction plaques
R-HSA-8867756 CLASP proteins and cargo are recruited to the nascent clathrin-coated pit
R-HSA-8868071 Clathrin recruits PIK3C2A
R-HSA-8868661 Dynamin-mediated GTP hydrolysis promotes vesicle scission
R-HSA-8868648 SYNJ hydrolyze PI(4,5)P2 to PI(4)P
R-HSA-8871194 RAB5 and GAPVD1 bind AP-2
R-HSA-8868658 HSPA8-mediated ATP hydrolysis promotes vesicle uncoating
R-HSA-8868659 Clathrin recruits auxilins to the clathrin-coated vesicle
R-HSA-8868660 Auxilin recruits HSPA8:ATP to the clathrin-coated vesicle
R-HSA-8867754 F- and N- BAR domain proteins bind the clathrin-coated pit
R-HSA-8868230 SNX9 recruits components of the actin polymerizing machinery
R-HSA-8868072 Clathrin-associated PIK3C2A phosphorylates PI(4)P to PI(3,4)P2
R-HSA-8868236 BAR domain proteins recruit dynamin
R-HSA-8868651 Endophilins recruit synaptojanins to the clathrin-coated pit
R-HSA-196025 Formation of annular gap junctions
R-HSA-8856825 Cargo recognition for clathrin-mediated endocytosis
R-HSA-190873 Gap junction degradation
R-HSA-8856828 Clathrin-mediated endocytosis
R-HSA-190828 Gap junction trafficking
R-HSA-199991 Membrane Trafficking
R-HSA-157858 Gap junction trafficking and regulation
R-HSA-5653656 Vesicle-mediated transport

-  Other Names for This Gene
  Alternate Gene Symbols: A6NES5, DAB2_HUMAN, DOC2, ENST00000320816.1, ENST00000320816.10, ENST00000320816.2, ENST00000320816.3, ENST00000320816.4, ENST00000320816.5, ENST00000320816.6, ENST00000320816.7, ENST00000320816.8, ENST00000320816.9, NM_001343, P98082, Q13598, Q9BTY0, Q9UK04, uc003jlx.1, uc003jlx.2, uc003jlx.3, uc003jlx.4, uc003jlx.5
UCSC ID: ENST00000320816.11
RefSeq Accession: NM_001343
Protein: P98082 (aka DAB2_HUMAN)
CCDS: CCDS34149.1, CCDS58946.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.