General Information of Target

Target ID LDTP05211
Target Name Disabled homolog 2 (DAB2)
Gene Name DAB2
Gene ID 1601
Synonyms
DOC2; Disabled homolog 2; Adaptor molecule disabled-2; Differentially expressed in ovarian carcinoma 2; DOC-2; Differentially-expressed protein 2
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MSNEVETSATNGQPDQQAAPKAPSKKEKKKGPEKTDEYLLARFKGDGVKYKAKLIGIDDV
PDARGDKMSQDSMMKLKGMAAAGRSQGQHKQRIWVNISLSGIKIIDEKTGVIEHEHPVNK
ISFIARDVTDNRAFGYVCGGEGQHQFFAIKTGQQAEPLVVDLKDLFQVIYNVKKKEEEKK
KIEEASKAVENGSEALMILDDQTNKLKSGVDQMDLFGDMSTPPDLNSPTESKDILLVDLN
SEIDTNQNSLRENPFLTNGITSCSLPRPTPQASFLPENAFSANLNFFPTPNPDPFRDDPF
TQPDQSTPSSFDSLKSPDQKKENSSSSSTPLSNGPLNGDVDYFGQQFDQISNRTGKQEAQ
AGPWPFSSSQTQPAVRTQNGVSEREQNGFSVKSSPNPFVGSPPKGLSIQNGVKQDLESSV
QSSPHDSIAIIPPPQSTKPGRGRRTAKSSANDLLASDIFAPPVSEPSGQASPTGQPTALQ
PNPLDLFKTSAPAPVGPLVGLGGVTVTLPQAGPWNTASLVFNQSPSMAPGAMMGGQPSGF
SQPVIFGTSPAVSGWNQPSPFAASTPPPVPVVWGPSASVAPNAWSTTSPLGNPFQSNIFP
APAVSTQPPSMHSSLLVTPPQPPPRAGPPKDISSDAFTALDPLGDKEIKDVKEMFKDFQL
RQPPAVPARKGEQTSSGTLSAFASYFNSKVGIPQENADHDDFDANQLLNKINEPPKPAPR
QVSLPVTKSTDNAFENPFFKDSFGSSQASVASSQPVSSEMYRDPFGNPFA
Target Bioclass
Other
Subcellular location
Cytoplasm
Function
Adapter protein that functions as a 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 containing 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.
Uniprot ID
P98082
Ensemble ID
ENST00000320816.11
HGNC ID
HGNC:2662

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 9 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
AZ-9
 Probe Info 
2.36  LDD0393  [1]
STPyne
 Probe Info 
K53(4.42)  LDD0277  [2]
DBIA
 Probe Info 
C138(3.30)  LDD3325  [3]
HHS-475
 Probe Info 
Y685(0.85); Y38(0.93); Y342(1.04)  LDD0264  [4]
5E-2FA
 Probe Info 
N.A.  LDD2235  [5]
m-APA
 Probe Info 
H425(0.00); H699(0.00)  LDD2231  [5]
IPM
 Probe Info 
N.A.  LDD2156  [6]
Acrolein
 Probe Info 
N.A.  LDD0217  [7]
HHS-465
 Probe Info 
Y170(0.00); Y685(0.00); Y342(0.00); K173(0.00)  LDD2240  [8]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0108  Chloroacetamide HeLa N.A.  LDD0222  [7]
 LDCM0116  HHS-0101 DM93 Y685(0.85); Y38(0.93); Y342(1.04)  LDD0264  [4]
 LDCM0117  HHS-0201 DM93 Y38(0.95); Y685(1.02); Y342(1.30)  LDD0265  [4]
 LDCM0118  HHS-0301 DM93 Y685(0.59); Y38(0.91); Y342(1.52)  LDD0266  [4]
 LDCM0119  HHS-0401 DM93 Y38(0.95); Y685(1.01); Y342(2.06)  LDD0267  [4]
 LDCM0120  HHS-0701 DM93 Y685(0.82); Y38(0.92); Y342(1.85)  LDD0268  [4]
 LDCM0022  KB02 A204 C138(1.71)  LDD2252  [3]
 LDCM0023  KB03 A204 C138(2.19)  LDD2669  [3]
 LDCM0024  KB05 UACC257 C138(3.30)  LDD3325  [3]
 LDCM0109  NEM HeLa H116(0.00); H114(0.00)  LDD0223  [7]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 2 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Superoxide dismutase [Cu-Zn] (SOD1) Cu-Zn superoxide dismutase family P00441
Unconventional myosin-VI (MYO6) Myosin family Q9UM54
Transporter and channel
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Amyloid-beta precursor protein (APP) APP family P05067
Transcription factor
Click To Hide/Show 2 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Mothers against decapentaplegic homolog 2 (SMAD2) Dwarfin/SMAD family Q15796
Mothers against decapentaplegic homolog 3 (SMAD3) Dwarfin/SMAD family P84022
Other
Click To Hide/Show 4 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Growth factor receptor-bound protein 2 (GRB2) GRB2/sem-5/DRK family P62993
Low-density lipoprotein receptor-related protein 6 (LRP6) LDLR family O75581
Epidermal growth factor receptor substrate 15 (EPS15) . P42566
SH2/SH3 adapter protein NCK1 (NCK1) . P16333

References

1 2H-Azirine-Based Reagents for Chemoselective Bioconjugation at Carboxyl Residues Inside Live Cells. J Am Chem Soc. 2020 Apr 1;142(13):6051-6059. doi: 10.1021/jacs.9b12116. Epub 2020 Mar 23.
2 A Paal-Knorr agent for chemoproteomic profiling of targets of isoketals in cells. Chem Sci. 2021 Oct 15;12(43):14557-14563. doi: 10.1039/d1sc02230j. eCollection 2021 Nov 10.
Mass spectrometry data entry: PXD028270
3 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840
4 Discovery of a Cell-Active SuTEx Ligand of Prostaglandin Reductase 2. Chembiochem. 2021 Jun 15;22(12):2134-2139. doi: 10.1002/cbic.202000879. Epub 2021 Apr 29.
5 Global profiling of functional histidines in live cells using small-molecule photosensitizer and chemical probe relay labelling. Nat Chem. 2024 Jun 4. doi: 10.1038/s41557-024-01545-6. Online ahead of print.
Mass spectrometry data entry: PXD042377
6 Benchmarking Cleavable Biotin Tags for Peptide-Centric Chemoproteomics. J Proteome Res. 2022 May 6;21(5):1349-1358. doi: 10.1021/acs.jproteome.2c00174. Epub 2022 Apr 25.
Mass spectrometry data entry: PXD031019
7 ACR-Based Probe for the Quantitative Profiling of Histidine Reactivity in the Human Proteome. J Am Chem Soc. 2023 Mar 8;145(9):5252-5260. doi: 10.1021/jacs.2c12653. Epub 2023 Feb 27.
8 Global profiling identifies a stress-responsive tyrosine site on EDC3 regulating biomolecular condensate formation. Cell Chem Biol. 2022 Dec 15;29(12):1709-1720.e7. doi: 10.1016/j.chembiol.2022.11.008. Epub 2022 Dec 6.
Mass spectrometry data entry: PXD038010