UniProt Accession

 DAB2_HUMAN; P98082; A6NES5; Q13598; Q9BTY0; Q9UK04 

Genbank Protein ID

 U39050; AH003698; U53446; AF188298; AF205890; AC008916; CH471119; BC003064; L16886 

Genbank Nucleotide ID

 AAC50824.1; AAB19032.1; AAA98975.1; AAF05540.1; AAF23161.1; EAW55989.1; AAH03064.1; AAA93195.1 

Protein Name

 Disabled homolog 2 

Protein Synonyms/Alias

 DOC-2; Differentially-expressed protein 2 

Gene Name

 DAB2 

Gene Synonyms/Alias

 DOC2 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
335	QISNRTGKQEAQAGP	ubiquitination	[1]

Reference

 [1] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661] 

Functional Description

 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. 

Sequence Annotation

 DOMAIN 45 196 PID.
 REGION 230 447 Required for localization to clathrin-
 REGION 604 732 Sufficient for interaction with GRB2 (By
 REGION 619 627 Required for interaction with CSK (By
 REGION 649 770 Required for interaction with MYO6 (By
 REGION 663 671 Required for interaction with GRB2 and
 REGION 709 725 Sufficient for interaction with SH3KBP1
 MOTIF 293 295 DPF 1.
 MOTIF 298 300 DPF 2.
 MOD_RES 2 2 N-acetylserine.
 MOD_RES 326 326 Phosphoserine; in mitosis (By
 MOD_RES 328 328 Phosphoserine; in mitosis (By
 MOD_RES 342 342 Phosphotyrosine (By similarity).
 MOD_RES 401 401 Phosphoserine.
 MOD_RES 729 729 Phosphoserine (By similarity).  

Keyword

 3D-structure; Acetylation; Alternative splicing; Apoptosis; Coated pit; Complete proteome; Cytoplasm; Cytoplasmic vesicle; Developmental protein; Differentiation; Endocytosis; Membrane; Phosphoprotein; Polymorphism; Protein transport; Reference proteome; Transport; Tumor suppressor; Wnt signaling pathway. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 770 AA 

Protein Sequence

Gene Ontology

 GO:0016324; C:apical plasma membrane; IEA:Compara.
 GO:0030132; C:clathrin coat of coated pit; IEA:Compara.
 GO:0030665; C:clathrin-coated vesicle membrane; IEA:UniProtKB-SubCell.
 GO:0005905; C:coated pit; IDA:UniProtKB.
 GO:0005765; C:lysosomal membrane; TAS:Reactome.
 GO:0005634; C:nucleus; IEA:Compara.
 GO:0005886; C:plasma membrane; TAS:Reactome.
 GO:0038024; F:cargo receptor activity; IMP:UniProtKB.
 GO:0035615; F:clathrin adaptor activity; IMP:UniProtKB.
 GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IEA:Compara.
 GO:0046332; F:SMAD binding; IDA:UniProtKB.
 GO:0007257; P:activation of JUN kinase activity; IEA:Compara.
 GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
 GO:0000904; P:cell morphogenesis involved in differentiation; IEA:Compara.
 GO:0008283; P:cell proliferation; TAS:ProtInc.
 GO:0016044; P:cellular membrane organization; TAS:Reactome.
 GO:0071560; P:cellular response to transforming growth factor beta stimulus; IEA:Compara.
 GO:0048268; P:clathrin coat assembly; IEA:Compara.
 GO:0007492; P:endoderm development; IEA:Compara.
 GO:0007588; P:excretion; IEA:Compara.
 GO:0001701; P:in utero embryonic development; IEA:Compara.
 GO:0030099; P:myeloid cell differentiation; IEA:Compara.
 GO:0060766; P:negative regulation of androgen receptor signaling pathway; IMP:UniProtKB.
 GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
 GO:0090090; P:negative regulation of canonical Wnt receptor signaling pathway; IMP:BHF-UCL.
 GO:0032091; P:negative regulation of protein binding; IMP:BHF-UCL.
 GO:0045892; P:negative regulation of transcription, DNA-dependent; IMP:BHF-UCL.
 GO:0006907; P:pinocytosis; IEA:Compara.
 GO:0030335; P:positive regulation of cell migration; IEA:Compara.
 GO:2000370; P:positive regulation of clathrin-mediated endocytosis; IMP:UniProtKB.
 GO:2000643; P:positive regulation of early endosome to late endosome transport; IMP:UniProtKB.
 GO:0010718; P:positive regulation of epithelial to mesenchymal transition; IDA:UniProtKB.
 GO:2001046; P:positive regulation of integrin-mediated signaling pathway; IEA:Compara.
 GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IDA:UniProtKB.
 GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:BHF-UCL.
 GO:0001921; P:positive regulation of receptor recycling; IEA:Compara.
 GO:0060391; P:positive regulation of SMAD protein import into nucleus; IDA:UniProtKB.
 GO:1900026; P:positive regulation of substrate adhesion-dependent cell spreading; IEA:Compara.
 GO:0032968; P:positive regulation of transcription elongation from RNA polymerase II promoter; IEA:Compara.
 GO:0045893; P:positive regulation of transcription, DNA-dependent; IMP:BHF-UCL.
 GO:0030511; P:positive regulation of transforming growth factor beta receptor signaling pathway; IDA:UniProtKB.
 GO:2000096; P:positive regulation of Wnt receptor signaling pathway, planar cell polarity pathway; IMP:BHF-UCL.
 GO:0015031; P:protein transport; IEA:UniProtKB-KW.
 GO:0016055; P:Wnt receptor signaling pathway; IEA:UniProtKB-KW. 

Interpro

 IPR011993; PH_like_dom.
 IPR006020; PTyr_interaction_dom. 

Pfam

 PF00640; PID 

SMART

 SM00462; PTB 

PROSITE

 PS01179; PID 

PRINTS